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

1 The ability of model stable epoxides and metabolites generated by human liver microsomes from benza[a]pyrene, anatoxin B-1, naphthalene and tamoxifen to produce cytotoxicity and genotoxicity in human peripheral lymphocytes has been investigated. 2 The stable epoxides 1,1,1 trichloropropene-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 naphthalene (100 mu M) by an extracellular metabolising system were toxic to isolated resting mononuclear leucocytes (MNLs), whereas glycidol (100 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 trans 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 dividing lymphocytes. Benzo[a]pyrene (100 mu M) and naphthalene (100 mu M) were not toxic either in the absence or presence of the extracellular 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 metabolising system. This indicates that both intracellular and extracellular bioactivation of these two compounds can produce genotoxicity. In contrast, naphthalene and tamoxifen were non-genotoxic.