Summation of initiation activities in the liver after partial hepatectomy.
Summation of initiation activities of different carcinogens in the liver after partial hepatectomy (PH) was investigated with reference to induction of glutathione S-transferase placental form (GST-P) positive foci. Firstly, effects of repeated administration of 1,2-dimethylhydradine (DMH) were compared with the results of a single administration of the same total dose (Expt. I). Subsequently, we studied summation of initiation potential with serial administration of DMH with diethylnitrosamine (DEN) or N-bis (2-hydroxpropyl)-nitrosamine (DHPN). In Expt. I, induction of GST-P-positive foci by multiple low-dose administration was equal to that with the single large-dose treatment. In order to avoid toxicity in hepatectomized rats, the low repeated-dose approach appeared superior. In Expt. II, the numbers of GST-P-positive foci in the groups treated with DMH plus DHPN or DMH plus DEN were significantly higher than those in the groups receiving the carcinogens singly. It is concluded that there is summation of initiation potential with doses of a single or multiple carcinogens. These results suggest that the present initiation assay model is useful to investigate summation of initiation activities of various environmental chemicals.
Sakai
Hiroki
H
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Tsukamoto
Tetsuya
T
Yamamoto
Masami
M
Hirata
Akihiro
A
Inagami
Atsushi
A
Shirai
Norimitsu
N
Iidaka
Takeshi
T
Yanai
Tokuma
T
Masegi
Toshiaki
T
Tatematsu
Masae
M
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens; D002455:Cell Division; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism* / Q000601:surgery*; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D009153:Mutagens; D009602:Nitrosamines; D010920:Placenta / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D007527:Isoenzymes; D009153:Mutagens; D009602:Nitrosamines; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496558:Gstp1 protein, rat; D019813:1,2-Dimethylhydrazine