Investigations of the genotoxicity and cell proliferative activity of dichlorvos in mouse forestomach.
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.
Benford
D J
DJ
Robens Institute of Industrial and Environmental Health and Safety, University of Surrey, Guildford, UK.
Price
S C
SC
Lawrence
J N
JN
Grasso
P
P
Bremmer
J N
JN
D000818:Animals; D002083:Butylated Hydroxyanisole / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects*; D004006:Dichlorvos / Q000633:toxicity*; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D013270:Stomach / Q000187:drug effects* / Q000473:pathology
D008769:Methylnitronitrosoguanidine; D002083:Butylated Hydroxyanisole; D004006:Dichlorvos