Cytochrome P-450 Monooxygenase Systems in Aquatic Species: Carcinogen Metabolism and Biomarkers for Carcinogen and Pollutant Exposure

Abstract

High levels of polynuclear aromatic hydrocarbon (PAH) carcinogens commonly occur in aquatic systems where neoplasms arise in fish and other animals. Enzymes that transform PAHs can act in initiating these diseases and can indicate the contamination of fish by carcinogens and other pollutants. Cytochrome P-450 has similar roles in activating PAH carcinogens in fish and mammalian species. PAHs and many chlorinated hydrocarbons, e.g., polychlorinated biphenyls (PCBs) induce a form of cytochrome P-450 in fish that is the primary catalyst of PAH metabolism. The induction of this P-450 in fish can accelerate the disposition of hydrocarbons, but can also enhance the formation of carcinogenic derivatives of PAHs. Invertebrates have lower rates of PAH metabolism than fish. These rates are not obviously inducible by exposure to PAHs or PCBs. The lower rates of foreign compound metabolism contribute to higher pollutant residue levels in bivalve mollusks (clams, mussels, etc.) than in fish and may limit the involvement of some procarcinogens (requiring activation) in disease processes in invertebrates. The induction of P-450 forms can indicate the exposure of fish to PAHs, PCBs, and other toxic compounds. This is not restricted to carcinogens. Environmental induction has been detected in fish from contaminated areas by use of catalytic assay, antibodies to fish P-450, and cDNA probes that hybridize with P-450 messenger RNA. Application of these methods can provide sensitive biological monitoring tools that can detect environmental contamination of fish by some carcinogens and tumor promoters.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcriptional expression analysis of ABC efflux transporters and xenobiotic-metabolizing enzymes in the Chinese rare minnow

“…These finding suggest that a common regulatory mechanism is possible for the GST, GCLC and ABCC genes (Meijerman et al, 2008). Furthermore, some of the phase I metabolites (e.g., B[a]P-7,8-diol-9,10-epoxide, the activated form of BaP) are suitable substrates for the GSTs (Stegeman and Lech, 1991;Christine Paetzold et al, 2009), and phase I and II metabolism makes many substances more suitable for export via the ABC transporters (Leslie et al, 2005). For example, arsenic-glutathione complex formation is required for the MRP2-mediated transport of arsenic into the bile (Kala et al, 2000), and sulfate conjugation of benzo[a]pyrene generates suitable ABCG2 substrates (Ebert et al, 2005).…”

DNA adduct formation and 7-ethoxyresorufin O-deethylase induction in primary culture of rainbow trout hepatocytes exposed to benzo[a]pyrene

“…Because of the involvement of P4501A in the activation of PAHs into their ultimate carcinogens, EROD might also be considered as a biomarker of the ability of a system to activate PAHs into DNAdamaging compounds (Stegeman and Lech, 1991). The primary culture of rainbow trout hepatocytes, in which EROD activity is inducible and DNA adducts are generated on exposure to B[a]P, enables the relationship between EROD activity and DNA adduct pattern and level to be examined.…”

“…A main P-450 responsible for PAH activation in rodents has been characterized as a member of the P450 1A subfamily, namely P4501 A1 (Ioannides and Parke, 1990). A fish P-450 implicated in PAH metabolism and activation is very similar to the rodent P4501AI form, particularly in its induction by planar compounds enhancing the metabolic activation of PAHs (Goksoyr et al, 1991;Stegeman and Lech, 1991). The P-450 inducible by planar xenobiotics in fish has been proposed as a biomarker of exposure to planar micropollutants (Stegeman and Lech, 1991).…”

Toxicological pathology of dab Limanda limanda along pollution gradients in the southern North Sea

“…These pathological methods of investigation, which were mainly limited to gross inspection, have revealed a variety of spatial and temporal trends in fish disease patterns in the North Sea (Bucke et al 1984, Bucke 1988, 1991, Bucke & Waterman 1988, Dethlefson 1988. This epidemiological type of approach can be complemented by the application of techniques which operate at the molecular, cellular and tissue level of organisation (Kohler 1989, Moore 1990, 1992a, b, Moore & Simpson 1991, Stegeman & Lech 1991, Varanasi & Stein 1991, Cameron & Berg 1992, Kohler et al 1992, Lowe et al 1992, Moore & Evans 1992. The combined methodology coupled with the use of supportive laboratory bioassays should help to define causal links between some classes of contaminant and specific types of toxic injury in fish.…”