Van Veld P A, Vogelbein W K, Smolowitz R, Woodin B R, Stegeman J J
College of William and Mary, School of Marine Science, Gloucester Point, VA 23062.
Carcinogenesis. 1992 Mar;13(3):505-7. doi: 10.1093/carcin/13.3.505.
The expression of cytochrome P450IA1 was examined in hepatic lesions of mummichog (Fundulus heteroclitus), a small, non-migratory teleost fish collected from a site in the Elizabeth River, VA, heavily contaminated with polycyclic aromatic hydrocarbons (PAH) of creosote origin. Immunoblot ('Western' blot) analysis using monoclonal antibody (MAb 1-12-3) to P450IA1 of the marine fish Stenotomus chrysops indicated that cytochrome P450IA1 levels in hepatocellular carcinoma and in foci of cellular alteration were 28-85% lower than those of adjacent non-neoplastic tissue. P450IA1-dependent monooxygenase activity, measured as ethoxyresorufin O-deethylase (EROD), exhibited a similar trend with EROD activity in lesions being 15-77% lower than activity in non-neoplastic tissue. Immunohistochemical examination of liver sections revealed general low intensity P450IA1-associated staining in hepatocellular carcinoma, exocrine pancreatic tissue, bile ducts and cholangiocellular proliferative lesions. Staining intensity of non-neoplastic hepatic parenchyma varied considerably and was focally distributed. In one case intense staining was observed in an altered hepatocellular focus (putative preneoplastic lesion). The results indicate important similarities in the expression of P450IA1 in neoplasms of fish and mammals and suggest an adaptive response of a wild population to carcinogen exposure.
对食蚊鱼（Fundulus heteroclitus）肝脏病变中的细胞色素P450IA1表达进行了检测。食蚊鱼是一种小型非洄游硬骨鱼，从弗吉尼亚州伊丽莎白河一处受杂酚油来源的多环芳烃（PAH）严重污染的地点采集。使用针对海洋鱼类金头鲷（Stenotomus chrysops）P450IA1的单克隆抗体（MAb 1-12-3）进行免疫印迹（“Western”印迹）分析表明，肝细胞癌和细胞改变灶中的细胞色素P450IA1水平比相邻的非肿瘤组织低28 - 85%。以乙氧异吩恶唑酮O - 脱乙基酶（EROD）衡量的P450IA1依赖性单加氧酶活性呈现类似趋势，病变中的EROD活性比非肿瘤组织中的活性低15 - 77%。肝脏切片的免疫组织化学检查显示，肝细胞癌、外分泌胰腺组织、胆管和胆管细胞增殖性病变中P450IA1相关染色强度普遍较低。非肿瘤性肝实质的染色强度差异很大且呈局灶性分布。在一个病例中，在一个改变的肝细胞灶（假定的癌前病变）中观察到强烈染色。结果表明鱼类和哺乳动物肿瘤中P450IA1表达存在重要相似性，并提示野生种群对致癌物暴露的适应性反应。
