Effects of single injection of methylazoxymethanol at postnatal day one on cell proliferation in different brain regions of male rats.
Methylazoxymethanol (MAM), an aglycone of cycasin extracted from Cycad seed, is reported to induce microencephaly in rats after prenatal or postnatal administration. Forty postnatal day (PND) 1 rats derived from 8 timed-pregnant rats were used to evaluate the effect of a single subcutaneous injection of MAM on PND 1 on cell proliferation in rat brain. All dams were fed NIH-31 diet. In the MAM-treated group, each pup received a single injection of MAM at 10 mg/kg body weight. In the control group, pups were injected with saline solution. Body weight of pups was recorded on PNDs 1, 7, 14, 21, 28, and 60. One male pup in each litter was removed for sacrifice by decapitation on PNDs 7, 14, 21, 28, and 60. The brain was removed and dissected to obtain the brain stem, caudate nucleus, cerebellum, frontal cortex, hippocampus, hypothalamus, and olfactory bulb. The percentage (%) of S-phase cells in the cell cycle for each region was measured as index of cell proliferation. A significant (p<0. 05) reduction in body weight was detected on PND 7. The % S-phase cells in cerebellum on PND 7 and olfactory bulb on PND 14 initially increased and then later decreased. There were significant decreases in the % S-phase cells in both cerebellum and caudate nucleus on PND 21 and olfactory bulb on PND 28. No significant changes were found in other brain regions in cell proliferation activity between the control and MAM-treated groups. The % of S-phase cells in cerebellum decreased 65% on PND 60 but lacked statistical significance due to small number of animals used in each group. The results indicated that a single injection of MAM at 10 mg/kg/body weight on PND 1 inhibited cell proliferation in the cerebellum in a manner that could lead to microencephaly.
National Center for Toxicological Research, Jefferson, AR 72079, USA. mlu@nctr.fda.gov
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D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity*; D008831:Microcephaly / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol