Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis.
Abstract
CYP1C1 is a relatively newly identified member of the cytochrome P450 family 1 in teleost fish. However, CYP1C1's expression and physiological roles relative to the more recognized CYP1A in polycyclic aromatic hydrocarbons (PAHs) induced toxicities are unclear. Fundulus heteroclitus fry were exposed at 6-8 days post-hatch (dph) and again at 13-15dph for 6h to dimethyl sulfoxide (DMSO) control, 5mg/L benzo[a]pyrene (BaP), or 5mg/L dimethylbenzanthracene (DMBA). Fry were euthanized at 0, 6, 18, 24 and 30h after the second exposure. In these groups, both CYP1A and CYP1C1 protein expression were induced within 6h after the second exposure. Immunohistochemistry (IHC) results from fry revealed strongest CYP1C1 expression in renal tubular and intestinal epithelial cells. Additional fish were examined for liver lesions 8 months after initial exposure. Gross lesions were observed in 20% of the BaP and 35% of the DMBA-treated fish livers. Histopathologic findings included foci of cellular alteration and neoplasms, including hepatocellular adenoma, hepatocellular carcinoma and cholangioma. Strong CYP1A immunostaining was detected diffusely in altered cell foci and on the invading margin of hepatocelluar carcinomas. Lower CYP1A expression ...Continue Reading
References
Trout P450IA1: cDNA and deduced protein sequence, expression in liver, and evolutionary significance
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