Effect of lindane on nitroreductase and dechlorinase enzyme activity in the gastrointestinal tract.
A previously reported acceleration of parathion metabolism in the gastrointestinal (GI) tract of lindane-pretreated rats could have been due to either a prolonged residence time of parathion or increased GI nitroreductase activity or both. Thus to determine the effect on GI nitroreductase and dechlorinase activity, 20 mg/kg lindane or 535 mg/kg neomycin were administered daily, by gavage, to weanling F-344 rats. Enzyme activity in the small intestine and cecum were assayed after 2 weeks and 5 weeks of treatment. Neomycin treatment inhibited the activity of both enzymes in the cecum but had no significant effect on enzyme activity in the small intestine, suggesting the presence of mucosal nitroreductase and dechlorinase in the small intestine. In contrast, lindane, which had no effect on enzyme activity in the cecum, significantly increased nitroreductase activity in the small intestine after treatment for 5 weeks. This increased nitroreductase may account for the previously reported lindane-parathion interaction and could influence the metabolism, toxicity, and risk assessment of many other environmental nitro-compounds that become toxic, mutagenic or carcinogenic upon reduction of their nitro-groups.
Chadwick
R W
RW
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Chang
J J
JJ
Gilligan
P H
PH
Forehand
L R
LR
Long
J E
JE
Duffy
M C
MC
D000818:Animals; D002432:Cecum / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D004347:Drug Interactions; D005260:Female; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D007421:Intestine, Small / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D008190:Lyases / Q000037:antagonists & inhibitors*; D009355:Neomycin / Q000494:pharmacology; D009601:Nitroreductases / Q000037:antagonists & inhibitors*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010278:Parathion / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D001556:Hexachlorocyclohexane; D010278:Parathion; D010088:Oxidoreductases; D009601:Nitroreductases; D008190:Lyases; C019990:DDT-dehydrochlorinase; D009355:Neomycin