Effects of endurance training on gene expression of insulin signal transduction pathway

Alternative splicing of insulin receptor mRNA and gene expression of insulin receptor, IRS-1 and MAP kinase isoforms were examined in skeletal muscle of trained and sedentary rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill: 30 m/min at 6 degrees incline, 90 min/day, 5 days/week. Endurance training increased insulin receptor mRNA level without change in alternative splicing of insulin receptor mRNA in skeletal muscle. The levels of IRS-1 and MAP kinase (ERKI) mRNA were significantly higher in trained rats than sedentary rats. Our findings provide the first evidence that gene expression of insulin receptor and postreceptor signal transduction pathway is enhanced by endurance training, without affecting alternative splicing of insulin receptor isoforms.     

Effects of fatigue and chewing training on maximal bite force and endurance

The purpose of the study was to evaluate the effects of chewing training on the strength and resistance to fatigue of the masticatory muscles. Twenty-five healthy adults were divided into an experimental group (7 men, 10 women) and a control group (4 men, 4 women). The experimental group chewed a special hard chewing gum one hour daily for 28 days. Maximal bite force and endurance were measured. The maximal bite force already showed a significant increase in the experimental group by the middle of the experimental period (p < 0.05), reached the highest values by the end of the training period (p < 0.001), and also remained at high levels 2 weeks after (p < 0.001). Subjects with weak initial maximal bite force values showed the highest increase in their strength after training (r = -0.66, p < 0.01). This type of training did not influence the endurance time during maximal clenching or the reduction in this endurance time after a dynamic fatigue test. No significant differences were found between the maximal bite force before and that after the fatigue test under either untrained or trained conditions. In the control group no significant differences were found between the recording sessions. In conclusion, 4 weeks training with a hard chewing gum seems to influence the functional capacity of the masticatory muscles and increase their strength.     

Effects of endurance training and heat acclimation on psychological strain in exercising men wearing protective clothing

Two experiments examined the influences of endurance training and heat acclimation on ratings of perceived exertion (RPE) and thermal discomfort (RTD) during exercise in the heat while wearing two types of clothing. In experiment 1, young men underwent 8 weeks of physical training [60-80% of maximal aerobic power (VO2max) for 30-45 min day-1, 3-4 days week-1 at 20-22 degrees C dry bulb (db) temperature] followed by 6 days of heat acclimation [45-55% VO2max for 60 min day-1 at 40 degrees C db, 30% relative humidity (rh)] (n = 7) or corresponding periods of control observation followed by heat acclimation (n = 9). In experiment 2, young men were heat-acclimated for 6 or 12 days (n = 8 each). Before and after each treatment, subjects completed bouts of treadmill exercise (1.34 m s-1, 2% grade in experiment 1 and 0% grade in experiment 2) in a climatic chamber (40 degrees C db, 30% rh), wearing in turn normal light clothing (continuous exercise at 37-45% VO2max for a tolerated exposure of 116-120 min in experiment 1 and at 31-34% VO2max for 146-150 min in experiment 2) or clothing protective against nuclear, biological, and chemical agents (continuous exercise at 42-51% VO2max for a tolerated exposure of 47-52 min in experiment 1 and intermittent exercise at 23% VO2max for 97-120 min in experiment 2). In experiment 1, when wearing normal clothing, endurance training and/or heat acclimation significantly decreased RPE and/or RTD at a fixed power output. There were concomitant reductions in relative work intensity (% VO2max) [an unchanged oxygen consumption (VO2) but an increased VO2max, or a reduced VO2 with no change of VO2max], rectal temperature (Tre), mean skin temperature (Tsk), and/or heart rate (HR). When wearing protective clothing, in contrast, there were no significant changes in RPE or RTD. Although training and/or acclimation reduced %VO2max or Tre, any added sweat that was secreted did not evaporate through the protective clothing, thus increasing discomfort after training or acclimation. Tolerance times were unchanged in either normal or protective clothing. In experiment 2, when wearing normal clothing, heat acclimation significantly decreased RPE and RTD at a fixed power output, with concomitant reductions in Tre, Tsk, and HR; the response was greater after 12 than after 6 days of acclimation, significantly so for RPE and HR. When wearing protective clothing, the subjects exercised at a lower intensity for a longer duration than in the moderate exercise trial. Given this tactic, either 6 or 12 days of heat acclimation induces significant reductions RPE and/or RTD, accompanied by reductions in Tre, Tsk, and/or HR. Tolerance times in protective clothing were also increased by 11-15% after acclimation, despite some increase of sweat accumulation in the protective clothing. The results suggest that (1) neither endurance training nor heat acclimation reduce psychological strain when protective clothing is worn during vigorous exercise, because increased sweat accumulation adds to discomfort, and (2) in contrast to the experience during more vigorous exercise, heat acclimation is beneficial to the subject wearing protective clothing if the intensity of effort is kept to a level that allows permeation of sweat through the clothing. This condition is likely to be met in most modern industrial applications.     

Effects of strength and endurance training on isometric muscle strength and walking speed in elderly women

The separate effects of 18 weeks of intensive strength and endurance training on isometric knee extension (KE) and flexion (KF) strength and walking speed were studied in 76- to 78- year-old women. Maximal voluntary isometric force for both KE and KF was measured in a sitting position on a custom-made dynamometer chair at a knee angle of 60 degrees from full extension. Maximal walking speed was measured over a distance of 10 m. The endurance-trained women increased KE torque and KE torque/body mass after the first 9 weeks of training when compared with the controls. when comparing the baseline, 9 week and 18 week measurements within the groups separately, both the endurance- and strength-training groups increased KE torque, KE torque/body mass and walking speed. Individual changes in KE torque/body mass before and after 18 weeks of training averaged 19.1% in the strength group, 30.9% in the endurance group and 2.0% in the controls. This study indicates that in elderly women the effects of physical training on muscle strength and walking speed occur after endurance as well as strength training. The considerable interindividual variation in change of muscle performance is also worth noticing.     

Effect of endurance training on pancreatic enzyme activity in rats

Immunoglobulin G (IgG) of Indian soft-furred rat, Millardia meltada, was purified by an immunoaffinity chromatography and antibodies against it was raised in rabbit. Using this rabbit anti-M. meltada IgG antibody, sensitivity of enzyme-linked immunosorbent assay (ELISA) to measure parasite-specific antibodies in the sera of M. meltada was markedly enhanced than the previous method using rabbit anti-mouse IgG and rabbit anti-rat IgG antibodies, which could cross-react to M. meltada IgG. Since M. meltada could effectively produce circulating antibodies against two intestinal helminths, Strongyloides venezuelensis and Nippostrongylus brasiliensis, the high susceptibility of this animal to an array of parasites seems to be not due to general immunological deficiency.     

Differential responses to endurance training in subsarcolemmal and intermyofibrillar mitochondria

To examine the effect of endurance training (6 wk of treadmill running) on regional mitochondrial adaptations within skeletal muscle, subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria were isolated from trained and control rat hindlimb muscles. Mitochondrial oxygen consumption (VO2) was measured polarographically by using the following substrates: 1 mM pyruvate + 1 mM malate (P+M), 10 mM 2-oxoglutarate, 45 microM palmitoyl-DL-carnitine + 1 mM malate, and 10 mM glutamate. Spectrophotometric assays of cytochrome-c reductase and NAD-specific isocitrate dehydrogenase (IDH) activity were also performed. Maximal (state III) and resting (state IV) VO2 were lower in SS than in IMF mitochondria in both trained and control groups. In SS mitochondria, training elicited significant 36 and 20% increases in state III VO2 with P+M and glutamate, respectively. In IMF mitochondria, training resulted in a smaller (20%), yet significant, increase in state III VO2 with P+M as a substrate, whereas state III VO2 increased 33 and 27% with 2-oxoglutarate and palmitoyl-DL-carnitine + malate, respectively. Within groups, cytochrome-c reductase and IDH activities were lower in SS when compared with IMF mitochondria. Training increased succinate-cytochrome-c reductase in both SS (30%) and IMF mitochondria (28%). IDH activity increased 32% in the trained IMF but remained unchanged in SS mitochondria. We conclude that endurance training promotes substantial changes in protein stoichiometry and composition of both SS and IMF mitochondria.     

Effect of endurance exercise training on muscle glycogen supercompensation in rats

The purpose of this study was to test the hypothesis that the rate and extent of glycogen supercompensation in skeletal muscle are increased by endurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for an additional 2 wk. Glycogen repletion was measured in trained and untrained rats after a glycogen-depleting bout of exercise. The rats were given a rodent chow diet plus 5% sucrose in their drinking water and libitum during the recovery period. There were remarkable differences in both the rates of glycogen accumulation and the glycogen concentrations attained in the two groups. The concentration of glycogen in epitrochlearis muscle averaged 13.1 +/- 0.9 mg/g wet wt in the untrained group and 31.7 +/- 2.7 mg/g in the trained group (P < 0.001) 24 h after the exercise. This difference could not be explained by a training effect on glycogen synthase. The training induced approximately 50% increases in muscle GLUT-4 glucose transporter protein and in hexokinase activity in epitrochlearis muscles. We conclude that endurance exercise training results in increases in both the rate and magnitude of muscle glycogen supercompensation in rats.     

Effect of endurance training on cardiac morphology in Alaskan sled dogs

The cardiac morphology of 77 conscious Alaskan sled dogs before and after 5 mo of endurance training (20 km/day team pulling a sled and musher) was studied using two-dimensional and M-mode echocardiography. Subgroups included dogs with at least one season of previous training ("veterans") and dogs undergoing their first season of training ("rookies"). Training resulted in a significant (P < 0.05) decrease in resting heart rate (-15%) and significant increases in interventricular septal thickness (systole, 15%; diastole, 13%), left ventricular (LV) internal dimension in diastole (LVIDd, 4%), LV free wall thickness in systole (9%) and diastole (LVWd, 9%), and left atrial diameter (5%) in all dogs, but the increase in LVWd was greater in rookies (16%) than in veterans (7%). Training increased end-diastolic volume index (8%), LV mass index (24%), and heart weight index (24%) and decreased the LVIDd-to-LVWd ratio (-6%) but did not alter cardiac index. We conclude that increased LV mass attributable to LV dilation and hypertrophy is associated with endurance training in Alaskan sled dogs. Disproportionate LV wall thickening accompanying LV dilation suggests that cardiac morphological changes are due to volume and pressure loading. These training-induced changes are similar to those documented in human athletes undergoing combined isometric and isotonic training and differ from studies of dogs trained on treadmills.     

Effects of acute endurance exercise and 8 week training on the production of reactive oxygen species from neutrophils in untrained men

The suboptimal efficacy of the currently available 23-valent pneumococcal vaccine in the growing population of adults >65 years old may be related to the limited immunogenicity of the vaccine polysaccharides in this group. In this study, the majority of elderly outpatients with stable chronic illnesses generated a vigorous IgG response to seven vaccine serotypes comparable to that of healthy young adults at 1, 3, and 16 months after immunization. Moreover, the quality and function of anticapsular antibodies, measured as avidity and in vitro opsonization, were comparable between elderly and young subjects over time. However, a subset (approximately 20%) of elderly outpatients responded to fewer than two of seven serotypes tested 1 and 3 months after immunization, whereas none of the healthy young adults were such poor responders. Thus, despite the adequate mean immune responses of the elderly as a group, a substantial proportion of elderly persons may have poor responses to the currently available pneumococcal vaccine.     

The case for adaptability of the neuromuscular junction to endurance exercise training

Although the adaptability of the neuromuscular junction (NMJ) has been demonstrated using the models of denervation/reinnervation, electrical stimulation, development, aging, and pathological states, relatively little is known about the effects of increased chronic voluntary use on the morphology and physiological function of the NMJ. A review of findings relating to adaptations in the various pre- and postsynaptic components of the NMJ with exercise training is presented. These findings are discussed as they pertain to NMJ function during exercise. Other physiological modulators of the NMJ, such as trophic factors released by nerve terminals and muscles, and circulating substances are discussed in terms of possible roles they may play in training-induced adaptations.     

Effect of training on some metabolic changes associated with submaximal endurance exercise in the horse

The effects of prolonged cantering before and after a 10 week training programme were studied in 6 horses. Determinations were carried on on venous blood for packed cell volume, glucose, glycerol, free fatty acids, beta-hydroxybutyrate, 11-hydroxycorticosteroids, pH and pCO2. Exercise caused a slight increase in glucose, lactate and pH, a moderate rise in PCV, glycerol and free fatty acids, and a marked rise in 11-hydroxycorticosteroids. A decrease in venous pCO2 occurred and a slight but not significant decrease in beta-hydroxybutyrate. Training was found to cause no significant difference in the changes seen. However, there was a tendency for exercise to result in higher 11-hydroxycorticosteroid levels after training.     

Effect of endurance training on fatty acid metabolism: local adaptations

Older studies of humans seem to suggest a correlation between free fatty acid (FFA) turnover and oxidation on the one hand and plasma FFA concentration on the other hand during submaximal exercise. However, recent studies, in which higher concentrations of plasma FFA have been reached during prolonged submaximal exercise, have revealed a levelling off in net uptake in spite of increasing plasma FFA concentrations. Furthermore, this relationship between FFA concentration and FFA uptake and oxidation is altered by endurance training. These recent findings in humans support the notion from other cell types that transmembrane fatty acid transport is not only by simple diffusion, but predominantly carrier-mediated. During prolonged submaximal knee-extension exercise it has been demonstrated that the total oxidation of fatty acids was approximately 60% higher in trained subjects than in nontrained subjects. The training-induced adaptations responsible for this increased utilization of plasma fatty acids by the muscle could be located at several steps from the mobilization of fatty acids to skeletal muscle metabolism in the mitochondria. In this paper regulation at the transport steps and also at various metabolic steps is discussed.     

Cardiovascular adaptations to endurance training and detraining in young and older athletes

A cross-sectional survey was carried out in a sugar estate in central Ethiopia to identify a subgroup for a cohort study on the natural history of HIV infection. HIV prevalence was 2.8% (95% confidence interval [CI], 1.7%-3.9%) in 957 adults aged 15 to 54 years randomly selected for the initial survey. A follow-up survey including only factory workers of the estate aged 18 to 45 years (n = 280) showed a higher HIV prevalence in male factory workers (n = 262) compared with the male estate workers of the same age of the initial survey (n = 484; 8.8% versus 3.1 %; p < .05). Factors independently associated with HIV infection in male factory workers were number of lifetime sexual partners, positive syphilis serology, higher income, and absence of travel outside the residential area. Among male estate workers, only older age was associated with HIV infection. Both factory workers and male estate workers were stable residents and were willing to participate in a long-term study on HIV/ AIDS. However, because of the higher HIV prevalence in factory workers and the higher prevalence of behaviors associated with an increased risk for HIV infection, factory workers were selected for the long-term cohort study on the natural history of HIV infection.     

Influence of posture and training on the endurance time of a low-level isometric contraction

Classically, the critical force of a muscle (the relative force below which an isometric contraction can be maintained for a very long time without fatigue) is comprised of between 15 and 20% of its maximum voluntary contraction (MVC). However, some authors believe that the value is below 10% MVC. If such is the case, signs that accompany the establishment of muscle fatigue (EMG changes, continuous increase in systolic blood pressure [SBP] and heart rate [HR]) would have to appear more rapidly and with a higher intensity if the muscle is already partially fatigued at the start of maintaining a contraction at 10% MVC. Twelve healthy untrained participants carried out two isometric contractions with the digit flexors: one (test A) began with a maximum contraction sustained for 4 min followed without interruption by a contraction at 10% MVC for 61 min; the other (test B) was a contraction maintained at 10% MVC for 65 min. For test B, after an initial increase of 4 bpm with respect to at rest, HR remained stable until the end of contraction, SBP progressively increased by 24 mm Hg in 28 min, then remained unchanged until the end, and there were no significant changes in EMG (absence of spectral deviation towards low frequencies). For test A, in spite of the initial maximum contraction, changes in the parameters being studied (total maintenance time, HR, SBP, EMG) during maintenance at 10% MVC were identical to those for test B. The results show that (1) when the number and intensity of the co-contractions are minimized by applying an appropriate posture, it is possible to sustain an isometric contraction at 10% MVC for at least 65 min without the appearance of signs of muscle fatigue; (2) the critical force of the digit flexors is higher than 10% MVC.     

Efficacy and position of endurance training as a non-drug therapy in the treatment of arterial hypertension

BACKGROUND: The prevalence of chronic lung disease increases with advancing age. The purpose of this study was to detect latent pulmonary hypertension noninvasively in elderly patients with chronic lung disease. METHODS: The changes of flow-velocity by passive leg raising were assessed using pulsed Doppler echocardiography in the right ventricular outflow tract in 19 patients with chronic lung disease and 13 normal healthy subjects. Pulmonary artery pressure was measured simultaneously using a thermodilution cardiac output catheter. RESULTS: In patients with chronic lung disease examined at rest, we found pulmonary hypertension in seven, and none in 12. The normal pattern observed at rest changed to pulmonary hypertension pattern after leg raising in six out of the 12 patients. Pulmonary arterial catheterization confirmed the data obtained by pulsed Doppler echocardiography. CONCLUSIONS: Some elderly patients with chronic lung disease have latent pulmonary hypertension which can be detected noninvasively by analyzing the changes of flow velocity profiles in the right ventricular outflow tract by passive leg raising.     

Gender-related differences in left ventricular filling dynamics in older subjects after endurance exercise training

The present study was designed to determine if gender affects the adaptive response to endurance exercise training of left ventricular filling dynamics in older individuals. Recently, it was shown that gender influences the cardiovascular responses to endurance exercise training in older subjects. Older men improve left ventricular systolic performance and increase maximal cardiac output in response to endurance exercise training, whereas older women do not. Twelve men (65 +/- 1 years old; mean +/- SE) and 10 women (64 +/- 1) were studied before and after 9 months of endurance exercise training. Maximal O2 uptake was determined during treadmill exercise. Left ventricular filling dynamics and ejection fraction (EF) at rest and during supine exercise were assessed by Tc-99m radionuclide ventriculography. When expressed relative to body weight, maximal O2 uptake (VO2 max) was increased by 24% (27.3 +/- 1.5 to 34.0 +/- 1.5 ml/kg/min; p < .01) in men and 27% (21.9 +/- 1.0 to 27.8 +/- 1.0 ml/kg/min; p < .01) in women in response to endurance exercise training. In men, the time-to-peak filling rate (TPFR) decreased (-19.8 +/- 6.7 ms; p < .05) during exercise at a comparable heart rate in response to training. In contrast, the change in TPFR in women (+2.7 +/- 6.0 ms) was small and insignificant. Peak filling rate (PFR) at rest and during exercise was similar before and after training in men and women. The change in left ventricular systolic reserve at a comparable heart rate from pre-to posttraining improved in men (delta EF 4 +/- 3%; p < .05), but not in women (-2 +/- 3%). The results indicate that the adaptive response of left ventricular filling dynamics to endurance exercise training is influenced by gender in older subjects. Older men show improvement in left ventricular filling dynamics, whereas older women do not.     

Influence of aging and endurance training on lactate dehydrogenase in liver and skeletal muscle

The purpose of this investigation was to determine the effects of aging and endurance training on lactate dehydrogenase (LDH) activity and isozyme pattern in liver and skeletal muscle. Male Fischer 344 rats (n = 30) of three different age groups (young, 4 months; middle-aged, 12 months and old, 22 months) were trained on a treadmill at 75% running capacity for 1 h/day, five times per week for 10 weeks. Age-matched sedentary controls (n = 36) were used for comparison. Total LDH enzyme activity was measured spectrophotometrically; LDH isozymes were separated by native 5.5% polyacrylamide gel electrophoresis and quantified densitometrically. With increasing age, hepatic LDH activity decreased 28%. Old sedentary animals displayed significantly less (22%) hepatic LDH 5 than young and middle-aged animals, and significantly more (40%) hepatic LDH 4 than middle-aged animals. Training resulted in a significant decrease (38%) in total hepatic LDH activity in young rats only. Young animals displayed a significant increase in hepatic LDH 3 (28%), whereas middle-aged animals exhibited a significant decrease in hepatic LDH 3 (40%) with training. No change in total hepatic LDH activity was exhibited in middle-aged or old rats with training. Neither aging or training had a significant effect on LDH activity or isozyme pattern in extensor digitorum longus (EDL). Similarly, LDH activity was maintained in soleus with age, and isozyme pattern was only negligibly affected. We conclude that with age there is a decline in hepatic LDH activity and a decrease in the LDH 5 isozyme. Endurance training induced significant decreases in hepatic LDH activity of young animals. However, these decreases were not a result of shifts in isozymal pattern. Further, LDH activity was maintained in EDL and soleus muscle with age. Finally, endurance training did not have a significant effect on LDH activity or isozymal pattern of EDL or soleus.     

Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise

The rates of increase in O2 uptake (VO2) after step changes in work rate from 25 W to 60% of pretraining peak VO2 (VO2 peak) were measured at various times during an endurance training program (2 h/day at 60% pretraining VO2 peak). Seven untrained males [23 +/- 1 (SE) yr] performed a series of repeated step changes in work rate before training (PRE) and after 4 days (4D), 9 days (9D), and 30 days (30D) of training. VO2 kinetic responses were determined from breath-by-breath data averaged across four repetitions and analyzed using a two-component exponential model. Mean response time (time taken to reach 63% of steady-state VO2) was faster (P < 0.01) than PRE (38.1 +/- 2.6 s) at both 4D (34.9 +/- 2.4 s) and 9D (32.5 +/- 1.8 s) and was faster (P < 0.01) at 30D than at all other times (28.3 +/- 1.0 s). Blood lactate concentrations (after 6 min of cycling) were also lower at 4D and 9D than PRE (P < 0.01) and were lower at 30D than at all other times (P < 0.01). VO2 peak was unchanged from PRE (3.52 +/- 0.20 l/min) at 8D (3.55 +/- 0.20 l/min) but was increased (P < 0.01) at 30D (3.89 +/- 0.18 l/min). Muscle oxidative capacity (maximal citrate synthase activity) was not significantly increased until 30D (P < 0.01). It is concluded that at least part of the acceleration of whole body VO2 kinetics with endurance training is a rapid phenomenon, occurring before changes in VO2 peak and/or muscle oxidative potential.     

The effect of strength and endurance training on gait, balance, fall risk, and health services use in community-living older adults

BACKGROUND: The study tested the effect of strength and endurance training on gait, balance, physical health status, fall risk, and health services use in older adults. METHODS: The study was a single-blinded, randomized controlled trial with intention-to-treat analysis. Adults (n = 105) age 68-85 with at least mild deficits in strength and balance were selected from a random sample of enrollees in a health maintenance organization. The intervention was supervised exercise (1-h sessions, three per week, for 24-26 weeks), followed by self-supervised exercise. Exercise groups included strength training using weight machines (n = 25), endurance training using bicycles (n = 25), and strength and endurance training (n = 25). Study outcomes included gait tests, balance tests, physical health status measures, self-reported falls (up to 25 months of follow-up), and inpatient and outpatient use and costs. RESULTS: There were no effects of exercise on gait, balance, or physical health status. Exercise had a protective effect on risk of falling (relative hazard = .53, 95% CI = .30-.91). Between 7 and 18 months after randomization, control subjects had more outpatient clinic visits (p < .06) and were more likely to sustain hospital costs over $5000 (p < .05). CONCLUSIONS: Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults. In community-living adults with mainly mild impairments in gait, balance, and physical health status, short-term exercise may not have a restorative effect on these impairments.     

Subcellular organization of the placenta in the Atlantic sharpnose shark, Rhizoprionodon terraenovae

Oncogenic transformation by human adenoviruses requires early regions 1A and 1B (E1A and E1B) and provides a model of multistep carcinogenesis. This study shows that the metabolic stabilization of p53 observed in adenovirus 5 (Ad5)-transformed cells can occur in untransformed cells expressing E1A alone. Stabilized p53 was localized to the nucleus and was indistinguishable from wild-type p53 with respect to its interactions with hsc70, PAb420, Ad5 p55E1B, and SV40 large T antigen. Moreover, binding of Ad5 p55E1B or SV40 large T antigen had no additional effect on p53 levels or turnover. Higher levels of p53 were also induced in a variety of cell types within 40 hr after transferring E1A genes. E1A also caused cells to lose viability by a process resembling apoptosis. The apoptosis appeared to involve p53, because p53 levels reverted to normal in surviving cells that had lost E1A, and E1B protected cells from the toxic effects of E1A. These results suggest that (1) the involvement of p53 in tumor suppression and/or apoptosis can be regulated at the level of protein turnover, and (2) a major oncogenic role for E1B is to counter cellular responses to E1A (i.e., stabilization of p53 and associated apoptosis) that preclude transformation by E1A alone. This represents the first physiological setting in which high levels of endogenous p53 are induced in response to an oncogenic challenge, with the apparent consequence of suppressing transformation.