Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.

Benzo[a]pyrene (B[a]P), a ubiquitous environmental, tobacco and dietary carcinogen, has been implicated in human cancer etiology. The role of human cytochrome P450 1B1 in the metabolism of B[a]P is poorly understood. Using microsomal preparations of human P450 1A1, 1A2 and 1B1 expressed in baculovirus-infected insect cells, as well as human and rat P450 1B1 expressed in yeast, we have determined the metabolism of B[a]P, with and without the addition of exogenous epoxide hydrolase, and B[a]P-7,8-dihydrodiol (7,8-diol), each substrate at a concentration of 10 microM. HPLC analysis detected eight major metabolites of B[a]P and four metabolites of the 7,8-diol. The results of these studies indicate that cytochrome P450 1B1 carries out metabolism of B[a]P along the pathway to the postulated ultimate carcinogen, the diol epoxide 2, at rates much higher than P450 1A2 but less than P450 1A1. The rates of formation of the 7,8-diol metabolite in incubations with epoxide hydrolase are 0.17 and 0.38 nmol/min/nmol P450 for human P450 1B1 and 1A1, respectively, and undetectable for 1A2. The rates of total tetrol metabolite formation from the 7,8-diol, which are indicative of diol epoxide formation, are 0.60, 0.43 and 2.58 nmol/min/nmol P450 for 1B1, 1A2 and 1A1 respectively. In agreement with other reports of rat P450 1B1 activity, our data show this rat enzyme to be very active for B[a]P and 7,8-diol, with rates higher than human P450 1B1. In addition to the established role of P450 1A1 in B[a]P metabolism, P450 1B1 may significantly contribute to B[a]P and 7,8-diol metabolism and carcinogenesis in rodent tumor models and in humans.

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To establish the relationship between ultraviolet-B radiation and squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK), a cross-sectional prevalence survey was performed in a sample of 808 white, male watermen 30 years of age and older residing in the Eastern Shore of Maryland. A measure of personal cumulative ultraviolet-B exposure was determined for each subject from data collected through interviews and field and laboratory measurements. A personal interview elicited skin type, medication history, and other factors. Clinical diagnoses and histologic confirmation were done for current and previously removed skin tumors. The ratio of subjects with SCC to subjects with BCC was approximately 1:1; however, the ratio of BCC to SCC was 1.25:l because BCC cases were more prone to multiple lesions. Watermen with SCC or AK but not BCC had higher average annual ultraviolet-B doses than age-matched controls. This was particularly marked in watermen younger than 60 years of age. Logistic regression showed that an older age, childhood freckling, and blue eyes significantly increased the risk of the development of all three types of skin tumor. Ease of sunburning was associated with BCC and AK, but not with SCC. Watermen in the upper quartile of cumulative ultraviolet-B exposure had a 2.5 times higher risk for the development of SCC when compared with the lower 3 quartiles. This suggests that high levels of ultraviolet-B exposure are important in SCC occurrence. The risk of AK developing was 1.5 times higher for those whose cumulative ultraviolet-B exposure exceeded the median. The relationship of BCC to cumulative ultraviolet-B exposure was not clear and this suggests that different etiologic mechanisms operate for SCC and BCC. Cancer 65:2811-2817,1990. From the