Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice

The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm.     

Study of platelet-activating factor acetylhydrolase in the perioperative period of patients undergoing cardiac surgery

This study was conducted to determine whether brief, intermittent exposure to hypoxia with little change in nutrient intake would affect fetal growth. Pregnant rats were exposed to 1 or 2 h of hypoxia (FiO2 = 0.09-0.095) from days 15 to 19 of gestation. Exposure to 1 h of hypoxia decreased fetal body weight and length, liver weight and increased the brain/liver weight ratio (p < 0.05) as compared to controls. Two hours of hypoxia decreased fetal body weight and length, and heart, lung, kidney, gut, brain and liver weights (p < 0.01), but did not affect the brain/liver weight ratio. Two hours of hypoxia decreased maternal food intake and weight gain (p < 0.05), but fetal growth was not significantly altered in pair-fed controls. These data demonstrate that brief, intermittent periods of intrauterine hypoxia have significant effects on fetal growth.     

Emotion and motivation: measuring affective perception

Fumonisin B1 (FB1), the major mycotoxin from Fusarium moniliforme, has been implicated as a causative agent in several animal and human diseases. Despite animal toxicity studies and human epidemiological studies of FB1, knowledge of its reproductive effects is scarce. In this study, one of a series of proposed studies that will allow extrapolation to humans, pregnant rats were given oral doses of 0, 1.875, 3.75, 7.5 or 15 mg FB1/kg on gestation days 3 16. Caesarean sections were performed on day 17 or 20, and maternal condition, implantation efficiency, foetal viability and foetal development were measured. Dose-related decreases in overall feed consumption and body weight gain were seen, but only the feed consumption decrease at 15 mg/kg, and the decreased body weight gain at 15 mg/kg on days 0-17 were statistically significant. Foetal body weights at day 17 were similar in control and treated groups; but in day-20 foetuses, female weight and crown-rump length were significantly decreased at 15 mg/kg. FB1 was not teratogenic at the doses tested, and no dose-related effects were seen in either skeletal or soft-tissue development. In day-17 animals, maternal and foetal brain, liver and kidney tissues, and maternal serum were preserved to study the levels of sphinganine (Sa), sphingosine (So), and the Sa/So ratios. Dose-related increases were seen in Sa/So ratios in maternal livers, kidneys and serum. Sa/So ratios of maternal brains were not affected, nor were those of foetal kidneys, livers or brains.     

Social class and health behaviour in Danish adults: a longitudinal study

In humans and animal models there is evidence that prenatal nicotine exposure causes lasting deficits in cognitive performance. The current study examined the cognitive effects of prenatal exposure of rats to 2 mg/kg/day of nicotine. This dose did not cause significant deficits in maternal weight gain, offspring litter size, or pup weight. The control offspring showed the normal ontogeny of spontaneous alternation from near chance (50%) performance to 80%-85% alternation. In contrast, the nicotine-exposed rats had the opposite progression with abnormally high alternation on days 22-30 and abnormally low alternation on days 35-52. Acquisition of choice accuracy performance on the radial-arm maze (RAM) was not altered in a major way by nicotine exposure. Minor nicotine-induced changes in choice accuracy were seen during the initial trials of acquisition. The nicotine exposed female offspring had a significantly longer response duration. Prenatal nicotine exposure did significantly alter the effects of subsequent drug challenges on choice accuracy performance. The nicotine-exposed male offspring were significantly more responsive to the amnestic effects of the nicotinic antagonist mecamylamine. In a subsequent challenge, the effects of the beta-adrenergic antagonist propranolol were examined. A significant dose-related impairment in choice accuracy was seen in the control rats. In contrast, the nicotine-exposed rats did not show any significant response to propranolol. This decreased responsiveness to adrenergic challenge parallels the reduction in adrenergic response to nicotine challenge we previously found in littermates to the rats of the current study. Prenatal nicotine exposure causes subtle alterations in cognitive performance that can be magnified by challenges of nicotinic and adrenergic systems.     

Inhalation teratology and reproduction studies with 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123)

HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and two-generation inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F1 generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F1 generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern. Since weight gain for the F1 animals was normal following weaning, this depression of body weight gain may be related to the depression of serum triglycerides. In addition, liver weights of the adult rats exposed to levels of 100 ppm and higher of HCFC 123 were higher than controls, histological examination revealed only hepatic enlargement and vacuolation. It was concluded that exposure to HCFC 123 did not cause reproductive effects although it did effect the body weight gain of the offspring during lactation.     

Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes

Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two-kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1 C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes.     

Cadmium accumulation in liver and kidney of mice exposed to the same weekly cadmium dose continuously or once a week

Cd levels in blood, liver and kidney of female mice were measured after exposure to Cd as CdCl2 in the food, either continuously (CE group) throughout the week (300 microg Cd/kg feed) or for 24 hr/wk (2100 microg Cd/kg) for 5 wk (occasionally exposed, OE group). In a control group that received feed with Cd levels below the detection limit (< 7 microg/kg), Cd levels in blood, liver and kidneys were below the detection limit after the 5 wk of exposure. The weekly dose of Cd administered to the exposed CE and OE groups was similar (approx. 400 microg Cd/kg mice/wk). The OE group had a higher Cd level in blood and a higher fractional accumulation (% of dose) of Cd in the liver and kidneys compared with the CE group. This indicates that the fractional Cd absorption in the gastrointestinal tract is higher when high Cd doses are ingested occasionally than when low doses are ingested continuously, even if weekly doses are the same. It is hypothesized that this difference in absorption could be due to Cd-induced unspecific damage to the intestinal mucosa, changes in tight-junction permeability caused by Cd, or to a saturation of the Cd-binding capacity of the intestinal mucosa in mice exposed to high Cd levels occasionally.     

Dual-mode presentation and its effect on implicit and explicit memory

Chronic exposure to methyl tertiary butyl ether (MTBE) altered the rodent tumor incidence of endocrine-sensitive tissues and decreased the incidence of estrogen-dependent uterine cystic hyperplasia in mice. To test the hypothesis that changes in the incidence of tumors in female B6C3F1 mice after MTBE exposure are secondary to endocrine alterations, we exposed female mice to the carcinogenic dose of MTBE vapor (8000 ppm) for 3 or 21 days or 4 or 8 months under conditions similar to a previous 2-year bioassay. MTBE exposure significantly decreased body weight gain and ovary and pituitary weight at 4 and 8 months and uterine weight at all time points. After 8 months of exposure, MTBE significantly increased the length of the estrous cycle by increasing the mean number of days in both the estrus and the nonestrus stages. Histological evaluation of H&E-stained tissues showed a decrease in the number of uterine glands after subchronic MTBE exposure. DNA synthesis, as measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU), was decreased in uterine glandular and luminal epithelial cells after MTBE exposure for 3 or 21 days or 4 or 8 months. MTBE exposure decreased the number of epithelial layers in the cervix and vagina at all time points. DNA synthesis was decreased in cervical and vaginal epithelium after 21 days of MTBE. Decreased zona reticularis of adrenal glands was found after 4 and 8 months of MTBE exposure without changes in BrdU incorporation. MTBE did not competitively bind to estrogen receptor. MTBE exposure did not alter serum estrogen levels or alter the location or intensity of estrogen receptor immunoreactivity in the uterus, cervix, and vagina. These data indicate that while MTBE exposure causes multiple endocrine-related tissue and cellular responses, these effects are not mediated through the estrogen receptor.     

Transgenic rabbits overexpressing growth hormone develop acromegaly and diabetes mellitus

Transgenic rabbits expressing the bovine growth hormone (bGH) gene in liver and kidney were obtained to study the long-term effects of chronic exposure to GH in nonrodent animals. These rabbits presented high levels of bGH and insulin-like growth factor I in serum. In spite of chronic exposure to bGH, transgenic rabbits had similar body weight to controls. However, enlargement of the head and limbs and reduction of visceral fat were observed in these animals. They also showed marked hyperinsulinemia, hyperglycemia, and hypertriglyceridemia, indicating that they developed insulin resistance. Furthermore, serious histopathological alterations, including marked fibrosis, were observed in liver, kidney, and skeletal muscle. These anatomical, metabolic, and histological alterations closely resemble those found in patients with acromegaly. Thus, transgenic rabbits overexpressing GH may be a good model of the human disease.     

Immunological evaluation of the mycotoxin patulin in female B6C3F1 mice

Patulin is a mycotoxin produced by many fungal species of the genera Penicillium, Aspergillus and Bryssochamys. Previous literature reports have suggested that patulin is toxic to the immune system. The studies presented were conducted to provide a comprehensive assessment of the effects of patulin on the immune system. Unlike previous reports, the doses of patulin used (0.08, 0.16, 0.32, 0.64, 1.28 and 2.56 mg/kg) were based on predicted human exposure levels. Female B6C3F1 mice were exposed orally to patulin for 28 days. Effects were not observed on final body weight or body weight gain. Relative weight of the liver, spleen, thymus, kidneys with adrenals, and lungs was not affected. Peripheral blood leucocyte and lymphocyte counts were decreased by approximately 30% in the two highest dose groups. The leucocyte differential was not altered. Total spleen cell, total T-cell (CD3+), helper T-cell (CD4+CD8-), B-cell (surface immunoglobulin+) and monocyte (MAC-3+) counts were not changed. Cytotoxic T-cell (CD8+CD4-) counts were increased 50% only by the highest dose. Natural killer cell (NK1.1+CD3-) and monocyte (MAC-1+) counts were increased 30% and 24%, respectively, only in the 0.08 mg/kg group. Humoral immune function as assessed by antibody-forming cell response and serum IgM titre to sheep erythrocytes, and cell-mediated immune function evaluated utilizing natural killer cell activity and the mixed lymphocyte reaction were not altered. Oral exposure to patulin for 28 days did not alter the ability of female B6C3F1 mice to mount either a cell-mediated or humoral immune response.     

A comparative study of 4 sequential first-line chemotherapy protocols in locally advanced breast cancer]

The toxic effect of Silesian air pollutants to mouse organs was examined. Histological changes were found in the examined lymphoid organs (thymus, spleen) as well nonlymphoid organs (liver, kidneys). The alterations in weight indexes of lymphoid organs were also observed. Considerable changes in cellularity, weight index, and histology of the thymus in the mice exposed to air pollutants suggest the atrophy of this organ, which may lead to extrathymic T-cell differentiation and even acceleration of thymocytes maturation, which may lead to certain allergic or auto-immune pollutants of all investigated mouse organs in the following order: thymus, liver, kidneys, and spleen.     

Health of tree swallows (Tachycineta bicolor) nesting in pesticide-sprayed apple orchards in Ontario, Canada. II. Sex and thyroid hormone concentrations and testes development

To investigate the effects of pesticides on wild birds, sex (17beta-estradiol; testosterone) and thyroid (triiodothyronine (T3) hormone concentrations, body mass, and testes mass were measured and the development of testes was evaluated in wild tree swallows (Tachycineta bicolor) nesting in four sprayed apple orchards and three nonsprayed sites in southern Ontario, Canada, in 1995-1996. In orchards, birds were exposed to asmany as 11 individual spray events and five sprays of mixtures of chemicals. Residues of organochlorine pesticides, PCBs, lead, and arsenic concentrations were low and not variable among sites except p,p'-DDE concentrations, which ranged from 0.36 to 2.23 microg/g wet weight in eggs. These persistent compounds were not correlated with any endocrine response measured in tree swallows. In 16-d-old male tree swallow chicks, body mass and concentrations of 17beta-estradiol (estradiol), testosterone, and T3 in plasma showed no significant differences between sprayed and nonsprayed groups and among sites within those groups. However, T3 concentrations were slightly elevated in the sprayed group compared to the nonsprayed group, and there was a significant and positive correlation between T3 and the number of mixtures of sprays applied during egg incubation through chick rearing. In 16-d-old female chicks, there were no significant differences among spray treatments or sites and no correlations with spray exposure for testosterone, estradiol, or T3 in plasma. Body mass was correlated positively with T3 and negatively with estradiol but showed no differences among spray exposure groups or sites. Histology of testes of 16-d-old male chicks indicated there were no significant differences among sprayed and nonsprayed birds in testes mass, area, or diameter, or the presence of Leydig cells in the interstitium, the distribution of the Sertoli cells, or the occurrence of heterophils in the testicular interstitium. For the percentage of spermatogonia present on the basement membrane, there were significant differences among sites, but these differences were not specifically associated with spray exposure. However, there was a marginally significant trend between increasing occurrence of a disrupted Sertoli cell population on the seminiferous tubular basement membranes as the number of mixtures of pesticides sprayed during chick rearing increased. In adult male and female parent tree swallows, there were no differences in hormone concentrations between birds from sprayed and nonsprayed sites. Nor were there any significant correlations between the concentration of any hormone and collection date, body mass, or any type of spray exposure for adults. The correlations between increasing pesticide exposure and abnormal thyroid hormone and testes development in male chicks indicate that further reductions of pesticide use in orchards may benefit the health of birds that nest there. However, it is unclear which of these pesticides or spray mixtures are responsible for these effects, and this needs to be examined in future studies.     

Toxicity of methylmercury chloride in rats. III. Long-term toxicity study

In the range-finding test, 6 groups of 4 male and 4 female weanling rats were given dietary levels of 0, 0.1,0.5, 2.5, 12.5 and 250 ppm methylmercury chloride (MeHgCl) for 2 weeks. Signs of central nervous system toxicity, weight loss and high mortality appeared at 250 ppm but not at lower levels. No haematological changes were observed at 0.1-12.5 ppm. The relative weights of the liver in females on 2.5 and 12.5 ppm and of the kidneys in females on 12.5 ppm were significantly increased; the effects in males were less marked. Total mercury concentration in the kidneys increased proportionally with increasing dietary levels of MeHgCl. In the short-term test, 5 groups of 15 male and 10 female weanling rats were given dietary levels of 0, 0.1, 0.5, 2.5 and 25 ppm MeHgCl for 12 weeks. Toxic signs, weight loss and restricted food intake were observed at 25 ppm starting from week 9 onwards. Haematological, serum enzyme and urinalysis changes were seen at 25 ppm. Liver microsomal enzyme activity was increased non-significantly and liver glycogen was depressed at 25 ppm. Organ weight changes were evident at 25 ppm and histological changes seen in the spleen, kidneys, brain, spinal cord and peripheral nerves were confined to the 25 ppm level. Histochemical changes in kidney enzymes occured at 2.5 and 25 ppm. Hg concentrations in blood, hair, kidneys, liver and brain were higher at 12 weeks than 6 weeks and generally increased with increasing MeHgCl level in the diet.     

The effects of thiamin on lead metabolism: organ distribution of lead 203

The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead administration, dose of thiamin and the specific treatment combination. Thiamin (25 or 50 mg/kg) treatment increased the whole body retention of both intragastric and intraperitoneal lead by approximately 10% in each instance. Calcium ethylenediaminetetraacetic acid, either alone or in combination with thiamin (50 mg/kg) reduced the whole body retention of lead by as much as 14% regardless of route of lead exposure. The relative retention of lead by the liver, kidney and spleen was greater in mice exposed to lead by the intragastric route. Regardless of route, CaEDTA in the combined treatment reduced the relative retention of lead in both the liver and kidney, whereas thiamin alone only reduced the retention of lead in the kidney. The results of this study indicate that thiamin in combination with CaEDTA alters the distribution and retention of lead in a manner which may have therapeutic application as it relates to chelation therapy.     

Recurrent aciclovir-resistant herpes simplex in a child with Wiskott-Aldrich syndrome

The possible cancer promotion potential of local exposure to a pulse modulated 929.2 MHz electromagnetic near-field on chemically-initiated rat liver carcinogenesis was investigated employing a medium-term bioassay. A 929.2-MHz electromagnetic near-field of time division multiple access (TDMA) signal for PDC (Personal Digital Cellular, Japanese cellular telephone standard) system was directed to rats through a quarter-wavelength monopole antenna. Maximum local specific absorption rates (SARs) on temporal average were 7.2-6.6 W/kg within the whole body and 2.0-1.7 W/kg within the liver, which was the target organ. The whole-body average SARs on temporal average were 0.80-0.58 W/kg. Temporal peak SARs had three times these values due to the duty ratio of the PDC signal. Exposure was for 90 min a day, 5 days a week, over 6 weeks. The exposure apparatus was specially designed for this experiment, to allow exposure of the lateral mid-section of the rat body to the electromagnetic near-field. Male F344 rats, 6 week-old, were initially (at week 0) given a single dose of diethylnitrosamine (DEN, 200 mg/kg body wt, i.p.). At 2 weeks later, exposure (48 rats) or sham-exposure (48 rats) was started. The exposure of electromagnetic near-fields was performed using the exposure apparatus mentioned above. At week 3, all rats were subjected to a 2/3 partial hepatectomy. At week 8 (i.e. after 6 weeks exposure or sham-exposure), the experiment was terminated and all rats were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P) positive foci in the livers of the exposed and sham-exposed rats. A further group of 24 animals, given only DEN and partial hepatectomy, served as the controls. The numbers (no./cm2) of GST-P positive foci were 4.61 +/- 1.77, 5.21 +/- 1.92 (P < 0.05, versus control) and 4.09 +/- 1.47 and the areas (mm2/cm2) were 0.30 +/- 0.16, 0.36 +/- 0.21 and 0.28 +/- 0.15, for the exposed, sham-exposed and control groups, respectively. There were no significant differences between the exposed and sham-exposed groups. These findings clearly indicated that local body exposure to a 929.2-MHz field, modulated in a PDC waveform, has no significant effect on rat liver carcinogenesis under the experimental conditions employed.     

Toxicity of fumonisin B1 to B6C3F1 mice: a 14-day gavage study

Fumonisin B1 (FB1) is a fungal toxin produced by members of the genus Fusarium. Ingestion of FB1 causes species-specific neurotoxic, nephrotoxic, hepatotoxic and pulmonary effects. The clinical, haematological and pathological responses of adult male and female B6C3F1 mice to FB1 were assessed following 14 daily gavage doses ranging from 1 to 75 mg FB1/kg body weight/day. There were no consistent sex-related changes. Although all responses were modest, the most notable effects of FB1 were on the liver, bone marrow, adrenals and kidneys. In the liver, hepatocellular single cell necrosis, mitosis and anisokaryosis were observed, accompanied by elevated serum ALT. In the kidneys, minor histopathological changes were confined to female mice, while mild decreases in ion transport and increases in blood urea nitrogen were seen only in males. Small changes in glutathione levels were observed in the kidneys and livers of male mice. Adrenal cortical cell vacuolation was observed at 15 mg FB1/kg and higher in females and from 35 mg FB1/kg in males. Serum cholesterol was elevated in both male and female mice, possibly due to FB1-induced changes in lipid metabolism in the liver and adrenals. Although bone marrow cell numbers were unchanged, increases in vacuolated myeloid cells and lymphocytes were observed in female mice. In general, the degree of changes observed indicate that mice are not as sensitive a model of FB1 toxicity as rats.     

Switching of chemoattractant receptors programs development and morphogenesis in Dictyostelium: receptor subtypes activate common responses at different agonist concentrations

Although uranium (U) is a classic experimental nephrotoxin, there are few data on its potential long-term chemical toxicity. These studies were undertaken to derive a no-observed-adverse-effect level (NOAEL) in male and female Sprague-Dawley rats following 91-day exposure to uranium (as uranyl nitrate hexahydrate, UN) in drinking water. Following a 28-day range-finding study, five groups of 15 male and 15 female weanling rats were exposed for 91 days to UN in drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). A control group was given tap water (< 0.001 mg U/L). Daily clinical observations were recorded. Following the study, animals were euthanized and exsanguinated, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and multiple tissues were sampled for histopathological examination. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Although there were qualitative and slight quantitative differences between males and females, histopathological lesions were observed in the kidney and liver, in both males and females, in all groups including the lowest exposure groups. Renal lesions of tubules (apical nuclear displacement and vesiculation, cytoplasmic vacuolation, and dilation), glomeruli (capsular sclerosis), and interstitium (reticulin sclerosis and lymphoid cuffing) were observed in the lowest exposure groups. A NOAEL was not achieved in this study, since adverse renal lesions were seen in the lowest exposed groups. A lowest-observed-adverse-effect level of 0.96 mg UN/L drinking water can be reported for both the male and the female rats (average dose equivalent 0.06 and 0.09 mg U/kg body wt/day, respectively).     

The validity of the Tritrac-R3D activity monitor for the assessment of physical activity: II. Temporal relationships among objective assessments

Today the organ donor operation in brain dead donors is mostly projected as multiple organ procurement (MOP). Not only the kidneys, but heart and liver or additionally lungs and pancreas are removed in MOP. A good synchronization between the collaborating transplantation groups (thoracic and abdominal surgeon, urologist) is essential to prevent loss of an organ because of technical problems. In Germany urologists perform more than 40% of kidney transplantations. These urologic institutions perform the cadaver kidney retrievals and participate on MOP. If possible, an urologist experienced in renal transplantation should contribute to the care for quality of the kidneys. Since 1987 the transplant center of Bremen obtained 390 donor registrations. 202 organ donor operations have been performed (106 MOP and 96 exclusive kidney retrievals). 398 donor kidneys have been collected and 382 could be transplanted.     

Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth

Quantitative trait loci (QTL) influencing body weight were mapped by linkage analysis in crosses between a high body weight selected line (DU6) and a control line (DUKs). The two mouse lines differ in body weight by 106% and in abdominal fat weight by 100% at 42 days. They were generated from the same base population and maintained as outbred colonies. Determination of line-specific allele frequencies at microsatellite markers spanning the genome indicated significant changes between the lines on 15 autosomes and the X chromosome. To confirm these effects, a QTL analysis was performed using structured F2 pedigrees derived from crosses of a single male from DU6 with a female from DUKs. QTL significant at the genome-wide level were mapped for body weight on chromosome 11; for abdominal fat weight on chromosomes 4, 11, and 13; for abdominal fat percentage on chromosomes 3 and 4; and for the weights of liver on chromosomes 4 and 11, of kidney on chromosomes 2 and 9, and of spleen on chromosome 11. The strong effect on body weight of the QTL on chromosome 11 was confirmed in three independent pedigrees. The effect was additive and independent of sex, accounting for 21-35% of the phenotypic variance of body weight within the corresponding F2 populations. The test for multiple QTL on chromosome 11 with combined data from all pedigrees indicated the segregation of two loci separated by 36 cM influencing body weight.