Effect of vitamin A status of rats on metabolizing enzymes after exposure to tobacco extract or N'-nitrosonornicotine.

The effects of N'-nitrosonornicotine (NNN) and tobacco extract on hepatic and pulmonary biotransformation enzymes were studied in rats fed vitamin A-sufficient or -deficient for semisynthetic diets. Basal levels of cytochrome P450, benzo[a]pyrene hydroxylase, benzphetamine demethylase, glutathione S-transferase and glutathione were lower in the group on the deficient diet. Treatment with tobacco extract or NNN significantly increased the levels of these enzymes in the sufficient diet group. However, in the deficient group, phase I enzymes were significantly increased, but glutathione and glutathione S-transferase levels were drastically reduced. Urine from animals on the deficient diet and treated with tobacco extract or NNN were mutagenic in the Ames Salmonella/microsome test. The results suggest that altered metabolism resulting from a vitamin A-deficient diet may be an important factor in susceptibility to carcinogens.