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DNA Adduct Formation by 7,12-Dimethylbenz(a)anthracene in Syrian Hamster Cheek Pouch Epithelium in Vivo¹

University of Connecticut Health Center, Department of Oral Diagnosis, Divisio of Oral Radiology, Farmington, Connecticut 06032

Studies examined the in vivo binding of radiolabeled 7,12-dimethyl-benz(a)anthracene (DMBA) to hamster cheek pouch epithelial DNA. Adduct formation was studied as functions of [³H]DMBA dose and of the time after single [³H]DMBA applications in mineral oil. Total DMBA-DNA adduct formation was determined by DNA-bound ³H activity, and qualitative binding characteristics were further studied by high-pressure liquid chromatography. Adduct formation 24 h after single [³H]DMBA applications rapidly increased from DMBA concentrations of 0.05–5.0 µg. While binding also increased from DMBA concentrations of 5.0–50.0 µg, the variability in adduct formation at 50.0 µg was considerable. Adduct formation following single 5.0-µg [³H]DMBA applications rose slowly to a peak value of 76 pmol DMBA/mg DNA at 36 h. This level decreased very slowly in a biphasic manner through 240 h, at which time the adduct levels were 23% of maximum. Adduct levels of 1.5 pmol/mg DNA were measured as late as 5 wk after a single 5.0-µg [³H]DMBA application. Chromatographic analyses of the 24-, 36-, and 96-, and 240-h samples showed three major peaks which are likely to be 1,2,3,4-tetrahydro-3,4-dihydroxy-1,2-oxide-deoxyribonucleoside adducts. While these analyses were limited by the small amounts of radioactivity which could be retrieved from [³H]DMBA-treated pouches, the study suggests that the DMBA-induced hamster cheek pouch carcinoma may be useful in some molecular in vivo studies of chemical-DNA interactions in carcinogenesis.

¹ Supported by Grants CA32991 and DE07713 from the Department of Health and Human Services, Public Health Service, National Cancer Institute. Guidelines for the care and use of laboratory animals were followed as set forth by the National Research Council.

² To whom reprint requests should be sent.

Received 3/18/85. Revised 8/17/87. Revised 11/20/87. Revised 12/23/87. Accepted 1/18/88.