Differences in the induction of SCEs between human whole blood cultures and purified lymphocyte cultures and the effect of an S9 mix.
Studies for SCE induction are frequently performed on human blood cultures. Either whole blood cultures (WBC) or purified lymphocyte cultures (PLC) are employed. However, it has been shown that fundamental differences with respect to metabolic activity exist between these two systems. In order to further characterize the whole blood culture and the purified lymphocyte culture, differently acting substances were studied comparatively with and without an Aroclor-1254-induced S9 mix. Treatment with ethyl methanesulfonate (EMS), a direct mutagen, produced distinct SCE induction in both systems. Cyclophosphamide (CP) and benzo[a]pyrene (BP), two indirect mutagens, also led to a significant increase of SCEs both in WBC and PLC without S9 mix. Only with CP was this effect more pronounced after addition of S9 mix. Sodium selenite (Na2SeO3), which induced SCEs in WBC, did not show this effect in the PLC. After S9 mix was added to purified lymphocytes, an increase of SCEs by sodium selenite was observed as in WBC. H2O2, a radical former, led to SCE induction in purified lymphocytes but not in the whole blood culture. By adding S9 mix, a distinct reduction of the SCEs induced by H2O2 was established. These results show that human lymphocytes can metabolize indirect mutagens and that it should be kept in mind when using S9 mix that, besides mixed-function oxygenases, it also contains enzymes which influence the SCE-inducing effects of substances.
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001711:Biotransformation; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003520:Cyclophosphamide / Q000633:toxicity; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects*; D020887:Selenious Acid; D012643:Selenium / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009153:Mutagens; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D006861:Hydrogen Peroxide; D020887:Selenious Acid; D012643:Selenium