INVESTIGATIONS OF THE GENOTOXICITY AND CELL PROLIFERATIVE ACTIVITY OFDICHLORVOS IN MOUSE FORESTOMACH

This study investigated the possible mechanism by which dichlorvos may have caused forestomach rumours in mice in a chronic corn oil gavage cancer bioassay [NTP (1989) Toxicology and carcinogenesis studies of d ichlorvos in F344/N rats and B6C3F1 mice (gavage studies). National To xicology Program Technical Report 342, NIH Publ. No 89-2598]. For this purpose, a method has been developed to assess the genotoxicity of ir ritant substances on mouse forestomach epithelium. Groups of five B6C3 F1 mice were given a single oral dose of dichlorvos, the genotoxic for estomach carcinogen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or the irritant, non-genotoxic forestomach carcinogen butylated hydroxyanisol e (BHA). After periods of 2-48 h, three parameters were assessed: unsc heduled DNA synthesis (UDS) by autoradiography of tissue sections, rep licative DNA synthesis (RDS) also by autoradiography of incorporated [ H-3]thymidine, and histopathological changes, including hyperplasia, M NNG induced UDS but not RDS or hyperplasia in forestomach epithelium, consistent with its genotoxic mode of action. BHA and dichlorvos did n ot induce UDS, consistent with absence of genotoxic activity in the fo restomach after in vivo exposure. In contrast, BHA and dichlorvos indu ced RDS and subsequent hyperplasia, which is likely to result from irr itant damage. These data suggest that the chronic effects of dichlorvo s on mouse forestomach epithelium in the oral gavage bioassay were med iated via enforced cell proliferation, rather than by a genotoxic mech anism.