Nicotine inhibition of the metabolism of 3,4-benzopyrene, a carcinogen in tobacco smoke.

A decreased rate of biliary excretion of radioactive metabolites of 3,4-benzopyrene was observed in rats given a single dose of nicotine. Prior treatment of rats with nicotine decreased benzopyrene hydroxylase activity in homogenates of liver, lung, and small intestine. The addition of nicotine to incubated tissues also decreased benzopyrene hydroxylase activity. These findings show that nicotine inhibits the metabolism of 3,4-benzopyrene in vivo and in vitro.

Natural toxicants in foods.

Food constitutes the most complex part of our chemical environment. Naturally occurring substances in food, such as goitrogens and estrogens, are toxicants. However, there is a difference of degree between toxicity and hazard, and the hazard to man in normal good health from naturally occurring toxicants in food is usually slight, because of (a) the small concentrations and (b) antagonistic interactions between toxicants which provide "safety in numbers." Hazard from foods may indeed exist under some circumstances, such as the presence of abnormal contaminants, ingestion of abnormal amounts, or abnormal susceptibility existing in some disease states. However, the major hazards of the dinner table can ordinarily be ascribed to careless food handling, unbalanced or fad diets, or overeating.

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.