We previously demonstrated that chemical carcinogens, benzo(a)pyrene and 7, 12-dimethylbenz-anthracene (DMBA) efflux mediated by the multidrug resistant (MDR) glycoprotein 170 (P-gp) in human breast cancer MCF-7 cells. We recently developed resistant human breast cancer cells resistant to benzo(a)pyrene (BP)by exposing them to increasing concentrations of this well known carcinogen. We found the BP resistant cells also were co- resistant to other carcinogen, e.g., DMBA but not to chemotherapeutic drugs, e.g. adriamycin, vinblastine. Importantly, this series of BP resistant MCF-7 cells neither express mdr RNA nor produced P-gp protein. From our findings we conclude that the mechanism for resisting the cytotoxicity of carcinogens is not due to P-gp-mediated carcinogen efflux. We carefully examined the biochemical and molecular changes in BP resistant cells and found the major changes are associated with repair mechanisms. A marked increase in enzyme activities and RNA expressions of glucose-6- phosphate dehydrogenase (G6PD), hypoxanthine-guanine phosphoribosyl transferase (HGPRT), and Topoisomerase II (Topo II) in BP resistant cells than carcinogen sensitive wild type cells. The implications of the increase in a glucose metabolic enzyme (G6PD), purine salvage pathway enzyme (HGPRT) and DNA repair enzyme (Topo II) are being investigated. Of special interest will be the regulation of these enzymes by dietary factors. We hope the understanding of carcinogen resistance in tissue culture cells will enhance our knowledge of this important mechanism in cancer prevention.
