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Age, Dietary Selenium and Quantity of 7,12-Dimethylbenz(a)anthracene Influence the in Vivo Occurrence of Rat Mammary DNA Adducts^1,2,

Department of Nutrition and The Graduate Program in Nutrition, The Pennsylvania State University, University Park, PA 16802

The present studies determined the impact of age, dietary selenium and 7,12-dimethylbenz(a)anthracene (DMBA) dosage on the occurrence of DMBA-DNA adducts in rat mammary tissue. Diets formulated to contain selenium, as sodium selenite, at 0.1 (control) or 2.0 mg/kg were fed for 2 wk before DMBA treatment. Food intake and weight gain were not influenced by selenium intake. Anti- and syn-dihydrodiol epoxide adducts reached maximum binding by 24 and 36 h, respectively, after treatment with DMBA. Consumption of the diet containing 2.0 mg Se/kg inhibited the appearance of both anti- and syn-adducts by 50% compared with controls. The occurrence of DMBA-DNA adducts correlated with a dosage of DMBA from 5 to 50 mg/kg body wt (r 0.95). The ability of supplemental selenite to lower DMBA binding to mammary cell DNA increased as the quantity of the carcinogen administered increased. DMBA-DNA binding was found to increase with the increasing age of the rat. Nevertheless, dietary selenium supplementation was effective in reducing DMBA binding to DNA in all ages examined. These data confirmed the ability of dietary selenium to inhibit the in vivo metabolism of DMBA under a variety of conditions.

KEY WORDS: • selenium • mammary DNA-adducts • 7,12-dimethylbenz(a)anthracene • rats • ³²P-postlabeling

¹ Supported in part by NIH, CA 44567.

² Presented at the annual meeting of the Federation of American Societies for Experimental Biology, April 1991, Atlanta, GA [Liu, J. & Milner, J. A. (1991) Influence of selenium, age, and dosage of 7,12-dimethylbenz(a)anthracene on the in vivo formation of DNA adducts in mammary tissue. FASEB J. 5: A927 (abs.)].

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 5 June 1991. Revision accepted 6 February 1992.