Pedrick, Michael Stephen; (1996) The activity of dietary beta-carotene against carcinogen-induced urinary bladder cancer in the rat. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The activity of dietary beta-carotene (BC) has been evaluated against urinary bladder cancer in rats treated with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). This experiment was designed to demonstrate whether any anti-cancer activity shown by BC was mediated through conversion to vitamin A, or through some other mechanism. Weanling female F344 rats were randomised into four dietary groups. Group 2 received a basic vitamin A-deficient diet which was supplemented with vitamin A. Group 1 also received the vitamin A-deficient diet supplemented with vitamin A until week 7, when 3 mM/kg BC was added. Groups 3 and 4 were fed the basic diet (without vitamin A supplementation) to week 7, at which time plasma vitamin A levels had fallen to approximately 10% of control values. Group 3 was then given 3 mM/kg BC, Group 4 received a low level of vitamin A supplementation in the drinking water, to maintain a healthy but vitamin A-deficient condition. At week 15, each group was divided into two; Groups 1-4 were dosed with BBN (a total of 635 mg/rat in 5 weekly aliquots), and Groups 5-8 received carcinogen vehicle. The animals were killed 42 weeks later. Urinary bladders were weighed, and total tumour volume/bladder calculated prior to histological examination. There was no statistically significant evidence that BC reduced the incidence of carcinomas, or relative bladder weights or tumour volumes in BBN-treated rats. Before this investigation could be undertaken, several other experiments were necessary. Three trials evaluated commercially-available vitamin A-deficient diets for use in the main experiment. Other studies were conducted to determine; 1) a method of maintaining vitamin A deficient rats for long-term experimentation, 2) that the absorption of appreciable amounts of unconverted BC by rats did occur, and 3) the survival of vitamin A-deficient rats following carcinogen treatment. To date, the present investigation into the activity of BC against carcinogen-induced urinary bladder cancer is the only one to be carried out in rats. Furthermore, it is the only experiment to have investigated the effect of BC against bladder cancer in vitamin A-normal and vitamin A-deficient animals. If the negative results reported here for BC against bladder cancer are repeated in other experimental systems, this may indicate that BC is not an effective chemopreventative agent for bladder cancer.

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