Lurie A G, Rozenski D L, Coghill J E
University of Connecticut Health Center, Department of Oral Diagnosis, Farmington 06032.
Cancer Res. 1988 Apr 15;48(8):2025-8.
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.
研究检测了放射性标记的7,12-二甲基苯并(a)蒽（DMBA）与仓鼠颊囊上皮DNA的体内结合情况。研究了加合物形成与[3H]DMBA剂量以及单次将[3H]DMBA涂抹于矿物油中后的时间之间的关系。通过DNA结合的3H活性来测定总的DMBA-DNA加合物形成情况，并通过高压液相色谱进一步研究其定性结合特征。单次应用[3H]DMBA 24小时后，加合物形成从DMBA浓度0.05 - 5.0微克迅速增加。虽然从DMBA浓度5.0 - 50.0微克时结合也增加，但50.0微克时加合物形成的变异性相当大。单次应用5.0微克[3H]DMBA后，加合物形成在36小时时缓慢上升至76 pmol DMBA/mg DNA的峰值。此水平以双相方式非常缓慢地下降，直至240小时，此时加合物水平为最大值的23%。在单次应用5.0微克[3H]DMBA后长达5周时，仍可检测到1.5 pmol/mg DNA的加合物水平。对24、36、96和240小时样本的色谱分析显示出三个主要峰，可能是1,2,3,4-四氢-3,4-二羟基-1,2-氧化物-脱氧核糖核苷加合物。虽然这些分析受到从[3H]DMBA处理的颊囊中可回收的放射性活度少量的限制，但该研究表明，DMBA诱导的仓鼠颊囊癌可能在化学致癌过程中一些化学物质与DNA相互作用的分子体内研究中有用。
