Effect of enzymatic induction and inhibition on cyclophosphamide-induced sister chromatid exchange in vivo.
The influence of the enzymatic inducer beta-naphthoflavone (BNF) and of the inhibitors alpha-naphthoflavone (ANF) and 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) on the frequency of sister chromatid exchanges (SCE) induced by cyclophosphamide (CPA) was studied in vivo in C57BL/6J male mice. Neither inducer nor inhibitors substantially modified the SCE level induced by 5 or 10 mg/kg CPA. The enzymatic induction by BNF was effective as treated animals showed a reduced paralysis time by zoxazolamine whereas ANF appeared to be ineffective. The enzymatic inhibition by SKF 525-A was confirmed by a longer sleeping time in pentobarbital-treated mice and also by a longer paralysis in zoxazolamine-treated mice. The lower susceptibility to CPA-induced SCEs of C57BL/6J mice relative to DBA/2 strain observed in a previous work seems not to be simply related to Ah locus mediated metabolism.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D015049:Zoxazolamine / Q000494:pharmacology; D019324:beta-Naphthoflavone
D001571:Benzoflavones; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D003520:Cyclophosphamide; D015049:Zoxazolamine; D011335:Proadifen; D006899:Mixed Function Oxygenases; C027270:cytochrome P448-dependent mono-oxygenase; D001973:Bromodeoxyuridine; D010424:Pentobarbital