EVALUATION OF THE GENERATION OF GENOTOXIC AND CYTOTOXIC METABOLITES OF BENZO[A]PYRENE, AFLATOXIN B-1, NAPHTHALENE AND TAMOXIFEN USING HUMANLIVER-MICROSOMES AND HUMAN-LYMPHOCYTES

1 The ability of model stable epoxides and metabolites generated by hu man liver microsomes from benza[a]pyrene, anatoxin B-1, naphthalene an d tamoxifen to produce cytotoxicity and genotoxicity in human peripher al lymphocytes has been investigated. 2 The stable epoxides 1,1,1 tric hloropropene-2,3-oxide (100 mu M) and trans stilbene oxide (100 mu M) as well as metabolites generated from anatoxin B-1 (30 mu M) and napht halene (100 mu M) by an extracellular metabolising system were toxic t o isolated resting mononuclear leucocytes (MNLs), whereas glycidol (10 0 mu M), benzo[a]pyrene (100 mu M) and tamoxifen (50 mu M) were not. 3 The stable epoxides 1,1,1 trichloropropene-2,3-oxide (100 mu M) and t rans stilbene oxide (100 mu M) but not glycidol (100 mu M) were toxic to dividing lymphocytes only after a 72-h exposure. Tamoxifen (30 mu M ), anatoxin B-1 (30 mu M) and their metabolites were also toxic to div iding lymphocytes. Benzo[a]pyrene (100 mu M) and naphthalene (100 mu M ) were not toxic either in the absence or presence of the extracellula r metabolising system. 4 Benzo[a]pyrene (100 mu M) and aflatoxin B-1 ( 30 mu M) were directly genotoxic to lymphocytes, this genotoxicity was significantly enhanced by the presence of the extracellular metabolis ing system. This indicates that both intracellular and extracellular b ioactivation of these two compounds can produce genotoxicity. In contr ast, naphthalene and tamoxifen were non-genotoxic.