Mohapatra N, MacNair P, Bryant B J, Ellis S, Rudo K, Sangaiah R, Gold A, Nesnow S
Mutat Res. 1987 Aug;188(4):323-34. doi: 10.1016/0165-1218(87)90009-7.
4 isomeric cyclopenta-derivatives of benz[e]anthracene (benz[a]aceanthrylene, benz[j]aceanthrylene, benz[l]aceanthrylene, and benz[k]acephenanthrylene) were examined for their ability to morphologically transform C3H10T1/2CL8 mouse-embryo fibroblasts. All of these polycyclic aromatic hydrocarbons studied except benz[k]acephenanthrylene transformed C3H10T1/2CL8 cells to both type II and type III foci in a concentration-dependent fashion. Benz[j]aceanthrylene was the most active, equivalent in activity to benzo[a]pyrene on a molar basis, in producing dishes of cells with transformed foci (94% at 1.0 microgram/ml). Benz[e]aceanthrylene, and benz[l]aceanthrylene produced 58% and 85% of the dishes with foci respectively at 10 micrograms/ml. Metabolism studies with [3H]benz[j]aceanthrylene in C3H10T1/2CL8 cells in which unconjugated, glucuronic acid conjugated, and sulfate conjugated metabolites were measured indicated that the dihydrodiol precursor to the bay-region diol-epoxide, 9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene, was the major dihydrodiol formed (55%). Smaller quantities of the cyclopenta-ring dihydrodiol, 1,2-dihydroxy-1,2-dihydrobenz[j]aceanthrylene (14%), and the k-region dihydrodiol, 11,12-dihydroxy-11,12-dihydrobenz[j]aceanthrylene (5%) were also formed. Similar studies with [14C]benz[l]aceanthrylene indicated that the k-region dihydrodiol, 7,8-dihydroxy-7,8-dihydrobenz[l]aceanthrylene was the major metabolite formed (45%). The cyclopenta-ring dihydrodiol, 1,2-dihydroxy-1,2-dihydrobenz[l]aceanthrylene and 4,5-dihydroxy-4,5-dihydrobenz[l]aceanthrylene were formed in minor amounts (less than 6%). Therefore, metabolism at the cyclopenta-ring of B(j)A and B(l)A is a minor pathway in C3H10T1/2CL8 cells in contrast to previously reported studies with cyclopenta[cd]pyrene in which the cyclopenta-ring dihydrodiol was the major metabolite. These results suggest that routes of metabolic activation other than oxidation at the cyclopenta-ring such as bay region or k-region activation may play an important role with these unique polycyclic aromatic hydrocarbons in C3H10T1/2CL8 cells.
研究了苯并[e]蒽的4种异构环戊二衍生物（苯并[a]醋蒽烯、苯并[j]醋蒽烯、苯并[l]醋蒽烯和苯并[k]醋菲烯）使C3H10T1/2CL8小鼠胚胎成纤维细胞发生形态转化的能力。除苯并[k]醋菲烯外，所有这些研究的多环芳烃均以浓度依赖的方式将C3H10T1/2CL8细胞转化为II型和III型集落。苯并[j]醋蒽烯活性最高，在产生有转化集落的细胞培养皿方面，摩尔活性与苯并[a]芘相当（1.0微克/毫升时为94%）。苯并[e]醋蒽烯和苯并[l]醋蒽烯在10微克/毫升时分别产生58%和85%有集落的培养皿。用[3H]苯并[j]醋蒽烯在C3H10T1/2CL8细胞中进行的代谢研究，测定了未结合、葡萄糖醛酸结合和硫酸结合的代谢物，结果表明，海湾区域二醇环氧化物的二氢二醇前体，9,10-二羟基-9,10-二氢苯并[j]醋蒽烯，是形成的主要二氢二醇（55%）。还形成了较少量的环戊环二氢二醇，1,2-二羟基-1,2-二氢苯并[j]醋蒽烯（14%）和k区域二氢二醇，11,12-二羟基-11,12-二氢苯并[j]醋蒽烯（5%）。用[14C]苯并[l]醋蒽烯进行的类似研究表明，k区域二氢二醇，7,8-二羟基-7,8-二氢苯并[l]醋蒽烯是形成的主要代谢物（45%）。环戊环二氢二醇，1,2-二羟基-1,2-二氢苯并[l]醋蒽烯和4,5-二羟基-4,5-二氢苯并[l]醋蒽烯形成量较少（小于6%）。因此，与先前报道的环戊[cd]芘研究不同，在C3H10T1/2CL8细胞中，苯并[j]醋蒽烯和苯并[l]醋蒽烯在环戊环的代谢是一条次要途径，在环戊[cd]芘研究中，环戊环二氢二醇是主要代谢物。这些结果表明，除了环戊环氧化之外的代谢活化途径，如海湾区域或k区域活化，可能在C3H10T1/2CL8细胞中这些独特的多环芳烃发挥重要作用。
