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Aberrant Activation of Benzo(a)pyrene in Cultured Rat Mammary Cells in Vitro and following Direct Application to Rat Mammary Glands in Vivo¹

Chester Beatty Laboratories, Institute of Cancer Research, Royal Cancer Hospital, Fulham Road, London SW3 6JB, England

Primary cultures of epithelial cell aggregates and fibroblasts derived from mammary tissue from female Wistar rats were treated with benzo(a)pyrene (BP), and their DNA was isolated and analyzed. At least seven BP-DNA adducts were detected in DNA hydrolysates by high-performance liquid chromatography, none of which had the chromatographic properties characteristic of adducts formed by the putative ultimate carcinogen r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BP-7,8-diol-9,10-oxide) or other known electrophilic metabolites of BP. Similar profiles of adducts were obtained from mammary DNA of rats that had been treated with BP by injection into their mammary fat pads. Chromatography on boronate columns indicated that five of the seven adducts contained cis-hydroxyl groups. In contrast, when BP was administered by i.p. injection to female Wistar rats, anti-BP-7,8-diol-9,10-oxide-DNA adducts were detected in each of seven tissues, including mammary gland, that were examined.

¹ This study was supported by grants from the United Kingdom Medical Research Council and Cancer Research Campaign.

Received 1/11/85. Revised 4/23/85. Accepted 4/30/85.

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