Hepatic cypiai expression and hepatic dna damage in tomcod from the hudson river

The presence of xenobiotics within tissues does not necessarily mean that they are biologically active. To address this issue, hepatic levels of CYP1A1 mRNA were compared between adult tomcod from the HR and four cleaner Atlantic Coast rivers. CYP1A1 expression is a widely used biomarker of exposure and early effect in fish because it is dose-responsively induced (increased) by exposure to environmentally relevant concentrations of PCDD/Fs, coplanar PCBs, and PAHs, and its encoded enzyme activities convert environmental PAHs to their active DNA-damaging metabolites. Also, the persistent induction of CYP1A1 by poorly metabolized PCDD/Fs/furans and PCBs generates reactive oxygen species which also damage DNA by generating modified bases (Schlezinger, White, and Stegeman, 1999). CYP1A1 expression may also be a biomarker of susceptibility to damage because of interindividual and interpopulation variation in its gene structure (Roy et al., 1995) and expression (Courtenay et al., 1994). CYP1A1 transcription is mediated through the aryl hydrocarbon receptor (AHR) - a signal transduction pathway whose activation mediates most, if not all, toxic responses to aromatic hydrocarbons in fishes (Hahn, 1998). Thus, induction of CYP1A1 serves as an easily quantifiable surrogate for complex toxic responses mediated by the AHR.

Hepatic CYP1A1 mRNA levels in adult tomcod from the HR were fifteen to twenty-two-fold higher than in those from the cleanest river tested (Wirgin etal., 1994). Additionally, environmentally exposed or chemically treated tomcod from the HR showed much higher levels of CYP1A mRNA expression than three other common anadromous HR species (Wirgin et al., 1996), a result that was consistent with the high prevalence of neoplasms in tomcod and their absence in the other species.

While induced levels of hepatic CYP1A1 are indicative of exposure to and bioactivity of PAHs, it may not always be predictive of increased hepatic DNA damage. To address this issue, the 32P post-labeling assay, a measure of DNA adducts levels, was used to compare hepatic DNA damage in adult tomcod from the HR and four cleaner estuaries. DNA adducts result from the binding of the reactive metabolites of PAHs and some other compounds to DNA. Levels of hepatic DNA adducts were approximately forty-fold higher in tomcod from the HR than in tomcod from the cleanest rivers tested (Wirgin et al., 1994) demonstrating that environmental agents, probably PAHs, were in fact incurring hepatic DNA damage to the HR population.

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