Distinction of carcinogens from mutagens by induction of liver cell foci in a model for detection of initiation activity.
Initiating activities of 26 chemicals were investigated in an in vivo 5 week initiation assay model with evaluation of the induction of glutathione S-transferase placental form (GST-P) positive foci as end-point lesions. With the five genotoxic hepatocarcinogens (diethylnitrosamine, dimethylnitrosamine, 2-acetylaminofluorene, N-bis(2-hydroxypropyl)-nitrosamine and safrole) and 11 genotoxic non-hepatocarcinogens, (2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, benzo[a]pyrene, N-butyl-N-(4-hydroxybutyl)nitrosamine, 7,12-dimethylbenz[a]anthracene, 1,2-dimethylhydrazine, N-ethyl-N-hydroxyethylnitrosamine, 3-methylcholanthrene, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide and 8-hydroxyquinoline), the numbers of GST-P positive foci were significantly higher than in the controls. On the other hand, the mutagenic non-carcinogens (quercetin, p-phenylenediamine dihydrochloride, 2-chloroethanol and 6-hydroquinoline) did not cause a significant increase. Similarly, non-genotoxic hepatocarcinogens of the hepatopromotor class and promotors which target organs other than the liver did not induce GST-P positive foci. The specificity was thus remarkable. Moreover, regardless of the target organ, mutagenic carcinogens were detected by this in vivo 5 week initiation assay, which therefore constitutes a powerful method for screening for carcinogenic potential, especially in the initiation stage of carcinogenesis.
Sakai
Hiroki
H
Division of Oncological Pathology, Research Institute, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.
Tsukamoto
Tetsuya
T
Yamamoto
Masami
M
Kobayashi
Kiyoshi
K
Yuasa
Hirofumi
H
Imai
Toshio
T
Yanai
Tokuma
T
Masegi
Toshiaki
T
Tatematsu
Masae
M
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D007527:Isoenzymes; D009153:Mutagens; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496558:Gstp1 protein, rat