Effect of the insecticides toxaphene and carbaryl on induction of lung tumors by benzo[a]pyrene in the mouse.
The insecticides toxaphene and carbaryl, when fed in the diet alone for 20 wk, were not tumorigenic to female A/J mice. Dietary levels of these insecticides were investigated for their effects on the incidence of lung tumors induced by oral administration of benzo[a]pyrene (BP). A significant reduction in BP-induced lung tumors was found after feeding 100 ppm toxaphene for 12 wk or 200 ppm for 20 wk. In contrast, 1000 ppm carbaryl fed for 20 wk caused a significant enhancement of BP-induced lung tumors. Mice that received toxaphene in the diet alone, or toxaphene and BP, showed an increase in BP hydroxylase activity in the liver and a decrease in enzyme activity in the lung. Carbaryl and BP increased BP hydroxylase activity in the lung without altering enzyme activity in the liver. Inhibition of lung BP hydroxylase activity was paralleled by a reduction in BP-induced lung tumors in mice fed toxaphene. Conversely, increased lung BP hydroxylase activity was associated with an enhancement of BP-induced lung tumors in animals fed carbaryl. The metabolism of BP by organs susceptible to BP-induced tumors and possible mechanisms for interactions with the insecticides are discussed.
D000818:Animals; D001564:Benzo(a)pyrene; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001580:Benzopyrenes / Q000633:toxicity*; D012721:Carbaryl / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008175:Lung Neoplasms / Q000139:chemically induced*; D051379:Mice; D008805:Mice, Inbred A; D009374:Neoplasms, Experimental / Q000139:chemically induced; D014112:Toxaphene / Q000494:pharmacology*
D001580:Benzopyrenes; D007306:Insecticides; D001564:Benzo(a)pyrene; D014112:Toxaphene; D001579:Benzopyrene Hydroxylase; D012721:Carbaryl