Hosomi J, Nemoto N, Kuroki T
Cancer Res. 1983 Aug;43(8):3643-8.
Genetic differences in metabolism of benzo(a)pyrene (BP) were investigated using cultured epidermal keratinocytes and dermal fibroblasts isolated from four inbred strains of mice: C3H/HeJms and C57BL/6J that are responsive; and DBA/2 and AKR/Jms that are nonresponsive in terms of inducibility of aryl hydrocarbon hydroxylase (AHH) activity. Primary cultures of epidermal and dermal cells isolated from newborn mice were treated with benz(a)anthracene for 24 hr. In both types of cells, AHH activity was induced in all four strains of mice, irrespective of their responsiveness in vivo. In the epidermal cells, basal AHH activity varied within a relatively small range of 4.6 to 8.8 pmol per mg protein per hr, and the activity was increased 4.4 to 8.7 times by benz(a)anthracene treatment. There was no difference in the extent of the induction in different strains of mice. In dermal cells, the basal level of AHH activity was in the range of 3.6 to 9.1 pmol per mg protein per hr, and benz(a)anthracene treatment induced AHH, but to various degrees depending on the responsiveness in vivo. Epidermal cells of the responsive mice metabolized more than 90% of the added BP in 48 hr, while those of nonresponsive mice metabolized only 60 to 70%. Dermal cells also metabolized BP, but to a lesser extent than did epidermal cells, and there was no strain difference in its metabolism. Time-course studies revealed that epidermal cells of responsive mice metabolized BP more rapidly than did those of nonresponsive mice. The activities of epidermal and dermal cells to metabolize BP were further demonstrated by a cell-mediated mutation assay. Consistent with the results of time-course analysis of the metabolites, shorter treatments with BP (less than 24 hr) showed a clear difference in BP metabolism associated with responsiveness.
利用从四种近交系小鼠中分离得到的培养表皮角质形成细胞和真皮成纤维细胞，研究了苯并(a)芘（BP）代谢的遗传差异：具有反应性的C3H/HeJms和C57BL/6J；以及在芳烃羟化酶（AHH）活性诱导方面无反应性的DBA/2和AKR/Jms。将从新生小鼠分离得到的表皮和真皮细胞原代培养物用苯并(a)蒽处理24小时。在这两种类型的细胞中，所有四株小鼠的AHH活性均被诱导，无论它们在体内的反应性如何。在表皮细胞中，基础AHH活性在每毫克蛋白质每小时4.6至8.8皮摩尔的相对较小范围内变化，并且苯并(a)蒽处理使活性增加了4.4至8.7倍。不同品系小鼠的诱导程度没有差异。在真皮细胞中，AHH活性的基础水平在每毫克蛋白质每小时3.6至9.1皮摩尔的范围内，苯并(a)蒽处理诱导了AHH，但程度因体内反应性而异。反应性小鼠的表皮细胞在48小时内代谢了超过90%的添加BP，而非反应性小鼠的表皮细胞仅代谢了60%至70%。真皮细胞也代谢BP，但程度低于表皮细胞，并且其代谢没有品系差异。时间进程研究表明，反应性小鼠的表皮细胞比非反应性小鼠的表皮细胞更快地代谢BP。细胞介导的突变试验进一步证明了表皮和真皮细胞代谢BP的活性。与代谢物的时间进程分析结果一致，用BP进行较短时间的处理（少于24小时）显示出与反应性相关的BP代谢存在明显差异。
