Carcinogenicity studies of tobacco extract in vitamin A-deficient Sprague-Dawley rats.

Long-term carcinogenicity studies were carried out in male Sprague-Dawley rats maintained on vitamin A-sufficient (SLO+) and vitamin A-deficient (SLO-) diets and treated with tobacco extract (TE). Three-week-old rats received by gavage a total dose of 860 mg of TE at a daily dose of 3 mg/rat over a period of 21 months. Besides tumorigenicity, drug-metabolizing phase I and phase II enzymes in lung and liver as well as vitamin A and C levels in plasma and liver were measured at 12 and 21 months of age.

Species differences in hepatic pulmonary and upper gastrointestinal tract biotransformation enzymes on long-term feeding of masheri--a pyrolyzed tobacco product.

The activities of several activating enzymes and that of glutathione S-transferase as well as levels of glutathione were measured in the upper alimentary tract, lung, and liver of Swiss mice, Sprague-Dawley rats, and Syrian golden hamsters treated with 10% masheri (pyrolyzed tobacco) in diet for 20 months. Significant increase in activities of phase I activating enzymes and a remarkable decrease in the phase II detoxification system in most extrahepatic tissues of the treated animals of all three species was observed. These observations suggest that the prolonged exposure to environmental xenobiotics/carcinogens affects the drug-metabolizing enzymes of the gastrointestinal tract, which may be an important factor in determining the susceptibility of different organs to carcinogen exposure.

Species difference in intestinal drug metabolising enzymes in mouse, rat and hamster and their inducibility by masheri, a pyrolysed tobacco product.

Activities of several drug metabolising enzymes in the small intestine were investigated in Swiss mice, Sprague Dawley rats and Syrian Golden Hamsters fed 10% masheri, a pyrolysed tobacco product, in diet, for 20 months. The basal levels of enzymes in proximal (PI), medium (MI) and distal (DI) parts of the intestine in the three species were similar. However, the levels of cytochrome P-450, benzo(a) pyrene hydroxylase (B(a)OH) and glutathione S-transferase (GST) were highest in hamsters followed by rat and mice.

Carcinogenicity studies of masheri: pyrolysed tobacco product, in vitamin-A-deficient Sprague Dawley rats.

The carcinogenicity of long-term feeding of masheri extract to animals in a vitamin-A-sufficient (SLO+) and deficient (SLO-) state was studied in Sprague Dawley rats by feeding daily dose of 3 mg extract over a period of 21 months. The phase I activating enzymes, the glutathione (GSH)/glutathione S-transferase (GST) detoxification system, and the hepatic and circulating levels of vitamins A and C were also monitored at 12 and 21 months. It was observed that the phase I enzyme activities were significantly higher in SLO+ than in SLO- rats at both 12 months and 21 months.

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.