Demonstration of initiation potential of carcinogens by induction of preneoplastic glutathione S-transferase P-form-positive liver cell foci: possible in vivo assay system for environmental carcinogens.
In a development trial for an initiation bioassay system, 7 known carcinogens and 1 suspected carcinogen were examined. In experiment 1, group 1 animals were initially subjected to partial hepatectomy (PH) 12 h before administration of diethylnitrosamine, 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), captafol, alpha-hexachlorocyclohexane or diethylstilbestrol (DES), then 2 weeks later underwent a promotion procedure comprising administration of phenobarbital (0.05% in diet) for 8 weeks and D-galactosamine (300 mg/kg, i.g.) at week 3. Group 2 received the promotion protocol alone as in group 1. Initiating potential was assayed on the basis of significant increase in values of preneoplastic placental form glutathione S-transferase-positive (GST-P+) foci of more than 3 cells in cross section at week 10. Numbers and areas of GST-P+ foci in group 1 given IQ, captafol and DES were significantly increased as compared to group 2, confirming the validity of the protocol as an initiation assay. In Experiment 2, group 1 rats were subjected to PH and 12 h later received a suspected carcinogenic mixture of opium pyrolysate (OP) or carcinogenic pesticide p,p'-dichloro-diphenyltrichloroethane or hexachlorobenzene. Application of a modified promotion procedure comprising cholic acid (0.15%) and carbon tetrachloride (1 ml/kg, i.g.) revealed significant initiation potential for OP. Overall the results indicate that the current protocols may be useful for detection of the initiation potential of carcinogens irrespective of their mutagenicity.
Tsuda
H
H
Second Department of Pathology, Fujita Health University School of Medicine, Aichi.
Matsumoto
K
K
Ogino
H
H
Ito
M
M
Hirono
I
I
Nagao
M
M
Sato
K
K
Cabral
R
R
Bartsch
H
H
D000818:Animals; D002215:Captan / Q000031:analogs & derivatives / Q000633:toxicity; D015197:Carcinogenicity Tests / Q000379:methods*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D053138:Cyclohexenes; D004052:Diethylnitrosamine / Q000633:toxicity; D004054:Diethylstilbestrol / Q000633:toxicity; D005659:Fungicides, Industrial / Q000633:toxicity; D005982:Glutathione Transferase / Q000032:analysis*; D001556:Hexachlorocyclohexane / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D011804:Quinolines / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D002274:Carcinogens, Environmental; D053138:Cyclohexenes; D005659:Fungicides, Industrial; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004052:Diethylnitrosamine; D001556:Hexachlorocyclohexane; D004054:Diethylstilbestrol; C001614:captafol; D005982:Glutathione Transferase; D002215:Captan