This study investigated the possible mechanism by which
dichlorvos may have caused forestomach tumours in mice in a chronic
corn oil gavage
cancer bioassay [NTP (1989) Toxicology and
carcinogenesis studies of
dichlorvos in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Technical Report 342, NIH Publ. No 89-2598]. For this purpose, a method has been developed to assess the genotoxicity of
irritant substances on mouse forestomach epithelium. Groups of five B6C3F1 mice were given a single oral dose of
dichlorvos, the genotoxic forestomach
carcinogen 1-methyl-3-nitro-1-nitrosoguanidine (
MNNG) or the
irritant, non-genotoxic forestomach
carcinogen butylated hydroxyanisole (
BHA). After periods of 2-48 h, three parameters were assessed: unscheduled
DNA synthesis (UDS) by autoradiography of tissue sections, replicative
DNA synthesis (RDS) also by autoradiography of incorporated [3H]
thymidine, and histopathological changes, including
hyperplasia.
MNNG induced UDS but not RDS or
hyperplasia in forestomach epithelium, consistent with its genotoxic mode of action.
BHA and
dichlorvos did not induce UDS, consistent with absence of genotoxic activity in the forestomach after in vivo exposure. In contrast,
BHA and
dichlorvos induced RDS and subsequent
hyperplasia, which is likely to result from
irritant damage. These data suggest that the chronic effects of
dichlorvos on mouse forestomach epithelium in the oral gavage bioassay were mediated via enforced cell proliferation, rather than by a genotoxic mechanism.