We have recently demonstrated, for the first time, molybdenum (Mo) supplementation significantly reduce the incidences of chemically induced esophageal and mammary cancers in rats, and tungsten (W) supplementation to counter the effect of Mo. The addition of Mo also significantly prolonged the estrous cycle. Our present plan is to attempt to elucidate the mechanism involved in the inhibitory effect of Mo on mammary carcinogenesis. Three animal experiments are designed. The first experiment is to determine the effect of graded levels of Mo supplementation on mammary carcinogenesis, while the second experiment is to investigate the timing of Mo supplementation on the inhibition of mammary carcinogenesis, and the third, the influence of dietary fat on the inhibitory effect of Mo on mammary carcinogenesis. Female weanling inbred Sprague-Dawley rats will be fed ad libitum for 30 weeks a nutritionally adequate semipurified (AIN-76) diet containing 0.026ppm Mo and 0.064 ppm W, and demineralized drinking water without or with Mo supplementation. At 50 days of age, animals will receive a single subcutaneous injection of 5 mg N-nitroso-N-methylurea (NMU)/100 g body weight. Four animals randomly selected from each experimental group will be transferred into individual metabolism cages for a 24-hour urine collection immediately prior to the initiation of the experiment, 24 hours after the NMU treatment and at weeks 7, 9, 11 and 30 of the experimental period. Immediately after the completion of urine collection, the animals will be sacrificed for the determination of (1) Mo-containing enzyme activities in liver, mammary gland and other tissues, (2) uric acid and other purine metabolites in plasma and urine, (3) metabolites associated with sulfite oxidase activity in plasma and urine, and (4) histopathological changes of mammary gland and other tissues. Emphasis will also be directed toward the effect of Mo supplementation on hormones and their receptors. For this, animals will be treated with the most optimal level and timing of Mo supplementation established in the above experiments. The timings of the carcinogen treatment and sacrifice will be adjusted individually so that the animals will be at the same stage of the estrous cycle. Plasma hormone contents and hormone receptors in the cytosol of mammary gland will be assayed.
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