Nyholm S H, Alexander J, Lundanes E, Frandsen H, Andersson R, Grivas S, Nesnow S, Holme J A
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Carcinogenesis. 1996 May;17(5):1111-20. doi: 10.1093/carcin/17.5.1111.
The biotransformation of benz[j]aceanthrylene (B[j]A) was studied in suspensions of hepatocytes isolated from Aroclor 1254-treated or untreated rats. Using radiolabeled cofactors and metabolic inhibitors combined with UV, mass and 1H-NMR spectroscopy, we have detected five known metabolites and characterized nine new metabolites: metabolite 1 was tentatively assigned as B[j]A-1,2-dihydrodiol-8-sulfate; metabolite 2, B[j]A-1,2,9,10-tetrahydrotetrol; metabolite 3, B[j]A-1,2-dihydrodiol-10-O-glucuronide; metabolite 4, B[j]A-1-one-8-sulfate; metabolite 5, B[j]A-1,2-dihydrodiol-10-sulfate; metabolite 6, the sulfate conjugate of B[j]A-dihydrodiol-phenol; peak 7 in the chromatogram is a mixture of one glutathione conjugate and two sulfate conjugates of a B[j]A-metabolite; metabolite 8, B[j]A-10-O-glucuronide; metabolite 8', B[j]A-1,2-dihydrodiol; metabolite 9, B[j]A-10-sulfate; metabolite 9', B[j]A-9,10-dihydrodiol and metabolite 10, B[j]A-9,10-dihydro-9-hydroxy-10-sulfate. The metabolites identified support the notion that epoxidation at the cyclopenta region is an important activation step of B[j]A. Furthermore, sulfation appears to play a very important role in the conversion of hydroxylated B[j]A metabolites into more polar excretable products.
在从经艾氏剂1254处理或未处理的大鼠分离出的肝细胞悬液中，研究了苯并[j]刺蒽（B[j]A）的生物转化。使用放射性标记的辅因子和代谢抑制剂，并结合紫外、质谱和1H-核磁共振光谱，我们检测到了五种已知代谢物，并对九种新代谢物进行了表征：代谢物1初步确定为B[j]A-1,2-二氢二醇-8-硫酸盐；代谢物2为B[j]A-1,2,9,10-四氢四醇；代谢物3为B[j]A-1,2-二氢二醇-10-O-葡萄糖醛酸苷；代谢物4为B[j]A-1-酮-8-硫酸盐；代谢物5为B[j]A-1,2-二氢二醇-10-硫酸盐；代谢物6为B[j]A-二氢二醇-苯酚的硫酸盐结合物；色谱图中的峰7是一种谷胱甘肽结合物与一种B[j]A代谢物的两种硫酸盐结合物的混合物；代谢物8为B[j]A-10-O-葡萄糖醛酸苷；代谢物8'为B[j]A-1,2-二氢二醇；代谢物9为B[j]A-10-硫酸盐；代谢物9'为B[j]A-9,10-二氢二醇；代谢物10为B[j]A-9,10-二氢-9-羟基-10-硫酸盐。所鉴定的代谢物支持了环戊区域的环氧化是B[j]A的一个重要活化步骤这一观点。此外，硫酸化在将羟基化的B[j]A代谢物转化为极性更强的可排泄产物的过程中似乎起着非常重要的作用。
