. The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BaP) is converted in the fish body (mainly in the liver and by cytochrome P-450) into potentially carcinogenic metabolites such as 7,8 dihydrodiol-9, 10-epoxide. In mammals, BaP has immunomodulatory effects and it is not known whether these effects are mediated by the unmetabolized parent compound or its metabolites. Fish possess some leukocytes that are able to recognize, bind and lyse tumor cell lines in vitro. Among these subpopulations, natural cytotoxic cells (NCC) recognize their target cells spontaneously, while antigen dependent cytotoxic cells (ACC) require previous exposure to the tumor cell antigen. As cytotoxic leukocytes are believed to play a major role in immunosurevelillance, it is possible that their activity may be modulated by carcinogens rendering them unable to recognize their target. Thus, the first objective of the proposed study is to determine if BaP or its metabolites are capable of modulating the NCC and ACC activities of the mummichog minnow Fundulus heteroclitus leukocytes. The standard chromium release assay will be performed at four different temperatures, as temperature was shown to effect BaP metabolism. Also the effects of BaP on some steps of the tumor cell lysis such as recognition, production of the cytotoxic factor(s) and cell death, will be studied. Another objective of this proposal will be to investigate in fish leukocytes are capable of metabolizing BaP and if this process is catalyzed by the cytochrome P-450 enzyme system. For this purpose, isolated minnow leukocytes (mixed and enriched) will be cocultured with BaP in the presence or absence of cytochrome P-450 inhibitory agents and the production of metabolites will be analyzed by HPLC.
| Rose, W L; French, B L; Reichert, W L et al. (2000) DNA adducts in hematopoietic tissues and blood of the mummichog (Fundulus heteroclitus) from a creosote-contaminated site in the Elizabeth River, Virginia. Mar Environ Res 50:581-9 |
