DNA adduct formation by 7,12-dimethylbenz(a)anthracene in Syrian hamster cheek pouch epithelium in vivo.
Studies examined the in vivo binding of radiolabeled 7,12-dimethylbenz(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 micrograms. While binding also increased from DMBA concentrations of 5.0-50.0 micrograms, the variability in adduct formation at 50.0 micrograms was considerable. Adduct formation following single 5.0-micrograms [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-micrograms [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.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000139:chemically induced; D013997:Time Factors
D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA