Enhancement by non-mutagenic pesticides of GST-P positive hepatic foci development initiated with diethylnitrosamine in the rat.
The potential hepatocarcinogenicity of seven pesticides was examined using a rapid bioassay based on the induction of glutathione S-transferase placental form positive foci in the rat liver. Rats were initially injected with diethylnitrosamine and two weeks later were fed on diet supplemented with one of the pesticides for 6 weeks and then killed; all rats were subjected to a partial hepatectomy at week 3. Positive results were seen with chlorobenzilate (2000 ppm), vinclozolin (2000 ppm), malathion (4000 ppm), tecnazene (2000 ppm) and isoproturon (2000 ppm). S,S,S-tributylphosphorotrithioate (DEF, 200 ppm) and dicloran (2000 ppm) were negative in both number and area analyses. Although chlorobenzilate is carcinogenic in mice, malathion and vinclozolin have been reported as non-carcinogens in both rats and mice. Since the present system is based on the two-stage carcinogenesis hypothesis, it is possible that the chemicals showing positive results in this system possess at least tumor-promoting activity in the rat liver. This is very significant, as most carcinogens show tumor-promoting activity in their target organs.
Hoshiya
T
T
First Department of Pathology, Nagoya City University Medical School, Japan.
Hasegawa
R
R
Hakoi
K
K
Cui
L
L
Ogiso
T
T
Cabral
R
R
Ito
N
N
D000818:Animals; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D010575:Pesticides; D004052:Diethylnitrosamine; D005982:Glutathione Transferase