Bhide S V, Ammigan N, Nair U J, Lalitha V S
Carcinogenesis Division, Tata Memorial Centre, Bombay, India.
Cancer Res. 1991 Jun 1;51(11):3018-23.
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.
对维持在维生素A充足（SLO +）和维生素A缺乏（SLO -）饮食的雄性Sprague-Dawley大鼠进行了长期致癌性研究，并给予烟草提取物（TE）处理。3周龄的大鼠在21个月的时间内，以每天3mg/只的剂量经口灌胃给予总量为860mg的TE。除了致瘤性外，还在12和21月龄时测量了肺和肝脏中的药物代谢I相和II相酶以及血浆和肝脏中的维生素A和C水平。经TE处理的SLO -大鼠的累积肿瘤发生率（77 - 100%）显著高于经TE处理的SLO +大鼠（20 - 22%）。此外，经TE处理的SLO +大鼠出现肺和前胃肿瘤，而经TE处理的SLO -大鼠则以垂体腺瘤为主（87%）。观察到，在两个时间点，TE处理均增加了SLO -大鼠肝脏和肺中I相酶的活性，并降低了谷胱甘肽/谷胱甘肽S -转移酶解毒系统的活性。TE处理后，肝脏和血浆中的维生素A水平显著降低，同时维生素C水平升高。数据表明，与维生素A充足的饮食相比，维生素A缺乏的饮食使雄性Sprague-Dawley大鼠对TE处理更敏感，这种效应与TE增强诱导P - 450含量和活性以及耗尽谷胱甘肽/谷胱甘肽S -转移酶途径有关。
