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. The cumulative tumor incidence in TE-treated SLO- rats was significantly higher (77-100%) than that observed in TE-treated SLO+ rats (20-22%). Furthermore, SLO+ rats treated with TE showed lung and forestomach tumors, whereas TE-treated SLO- rats showed a preponderance of pituitary adenomas (87%). It was observed that TE treatment increased the activity of the hepatic and pulmonary phase I enzymes and decreased the glutathione/glutathione S-transferase detoxification system at both time points in SLO- rats. On TE treatment the vitamin A levels in the liver and plasma were significantly decreased with a concurrent increase in vitamin C levels. The data show that a vitamin A-deficient diet renders male Sprague-Dawley rats more susceptible to TE treatment than the vitamin A-sufficient diet, an effect which was associated with the augmented induction of P-450 content and activities and depletion of the glutathione/glutathione S-transferase pathway by TE.
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Carcinogenesis Division, Tata Memorial Centre, Bombay, India.
Ammigan
N
N
Nair
U J
UJ
Lalitha
V S
VS
D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D004121:Dimethyl Sulfoxide; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000139:chemically induced; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D010212:Papilloma / Q000139:chemically induced; D010911:Pituitary Neoplasms / Q000139:chemically induced; D010936:Plant Extracts / Q000633:toxicity; D010947:Plants, Toxic; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms / Q000139:chemically induced; D014026:Nicotiana; D014802:Vitamin A Deficiency / Q000150:complications*
D010936:Plant Extracts; D004121:Dimethyl Sulfoxide