Date of Award:
Master of Science (MS)
William A. Brindley
William A. Brindley
R. P. Sharma
James L. Shupe
Microtus sp. have been used in microcosm simulations of polluted environments. In this study, female Microtus montanus (mountain vole), 8 - 12 weeks of age, were pretreated with phenobarbital (PB), ß-naphthoflavone (BNF), or Aroclor 1254 (PCB) for 3 consecutive days. Doses ranged from 5 to 80 mg/kg for each pretreatment, while control animals received saline or corn oil only. The voles were sacrificed 1 day after the last dose of PB and 2 days after BNF and PCB. Hepatic microsomal enzyme activity of aniline hydroxylase (AH), p-nitroanisole-O-demethylase (PNA) and cytochrome C reductase (CCR) were measured in relation to dose and type of inducer pretreatment. PB produced an induction for all 3 enzyme systems at the higher doses. Variation of PB dose from 5 to 80 mg/kg produced a biphasic effect in AH, PNA increased with each higher dose, and CCR showed a triphasic effect. BNF caused no significant change in AH activity, a biphasic response in PNA, and a triphasic effect in CCR with the highest activity at the 20 mg/kg dose. PCB demonstrated slight induction at low doses but higher doses produced no change or a decrease in enzyme activity. No increase in SGPT levels or serum malathion carboxylesterase occurred. Histological investigations revealed 2 morphological phases related to the type of induction. Low level induction showed foamy, vacuolated hepatocytes, while high induction produced very large, hypertrophied hepatocytes. A positive control for hepatic necrosis using 0.1 ml/kg carbon tetrachloride showed significant increases in serum enzymes and severe centrilobular and midzonal acute hepatic necrosis. Therefore, these results show a difference in induction potential of BNF and PCB compared to other rodents. Also, this study indicates the importance of inducer dose on the effect of hepatic monooxygenase activity.
Hincks, Jeffrey Robert, "Alteration in Serum Enzyme Levels, Activity of Hepatic Monooxygenases, and Hepatocyte Morphology Due to Liver Enzyme Inducers in Microtus montanus" (1983). All Graduate Theses and Dissertations. 8311.
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