Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21-day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 +/- 2.0), 4 (12.3 +/- 1.2) and 5 (8.7 +/- 0.9) in relation to controls (10.6 +/- 1.2; 4.5 +/- 0.6 and 3.4 +/- 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 +/- 11) and 17 (124 +/- 12), and 16 (104 +/- 9), 17 (137 +/- 9) and 18 (106 +/- 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 +/- 11 and 69 +/- 10 for days 16 and 17 and 49 +/- 9, 48 +/- 7 and 56 +/- 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.     

Bcl-2 family proteins

Bcl-2 family proteins serve as critical regulators of pathways involved in apoptosis, acting to either inhibit or promote cell death. Altered expression of these proteins occurs commonly in human cancers, contributing to neoplastic cell expansion by suppressing programmed cell death and extending tumor cell life span. Moreover, because chemotherapeutic drugs typically exert their cytotoxic actions by inducing apoptosis, the ultimate efficacy of most anticancer drugs can be heavily influenced by the relative levels and state of activation of members of the Bcl-2 family. The question of how Bcl-2 family proteins function remains debatable, but new findings are shaping our impressions of these multi-functional proteins and revealing the details of how these proteins participate in the regulation of cell life and death.     

Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria

Apoptotic cell death involves a ritual series of morphological changes, presumably reflecting a conserved molecular pathway. We now report that the nuclear events typical of apoptosis can be reproduced in "apoptotic" Xenopus egg extracts. In this cell-free system, nuclear assembly and protein import are initially normal; after 2-4 hr, however, a process of nuclear destruction ensues involving chromatin condensation and the shrinkage and fragmentation of the nuclei. This apoptotic process, which also occurs in nuclei added exogenously, is blocked by the addition of baculovirus-expressed Bcl-2 protein. To block the disintegration of nuclei that are added later, Bcl-2 must be present during this latent period. "Apoptosis" in these extracts requires a dense organelle fraction enriched in mitochondria. The cell-free system described here provides a novel tool for understanding intracellular events in apoptosis and the inhibitory function of Bcl-2.