Summation of initiation activities of low doses of the non-hepatocarcinogen 1,2-dimethylhydrazine in the liver after carbon tetrachloride administration

Hiroki Sakai, Tetsuya Tsukamoto, Masami Yamamoto, Tokuma Yanai, Toshiaki Masegi, Ken Ichi Inada, Hayao Nakanishi, Masae Tatematsu

研究成果: Article査読

20 被引用数 (Scopus)

抄録

Summation of initiation by low doses of the indirect-acting non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) after proliferative stimulation with a necrogenic dose of carbon tetrachloride (CCl4) was investigated in terms of the induction of glutathione S-transferase placental form (GST-P) positive liver cell foci. Cell kinetics of liver after CCl4 i.g. treatment were examined with bromodeoxyuridine (BrdU) labeling (experiment I). To assess the correlation between cell proliferation and induction of liver cell foci, DMH (10 mg/kg i.g.) was administrated to 7-week-old male F344 rats at 12, 24, 36, 48, 60, 96 h after CCl4 i.g. and initiated populations expanded using the resistant hepatocyte model (experiment IIA). Subsequently, effects of repeated administration (10 mg/kg, four times, i.g.) of DMH were compared with the results of a single administration (40 mg/kg, i.g.) with the same total dose (experiment IIB). In experiments I and IIA, the numbers and areas of GST-P-positive foci increased with the BrdU labeling index at the time of DMH treatment (maximum after 60 h). In experiment IIB, repeated exposure of DMH at 10 mg/kg, four times resulted in significant (P<0.05) increase in number and area of GST-P-positive foci compared with the single administration (40 mg/kg). Thus, multiple low dose treatments during cell proliferation might be most effective for detection of weak initiation activity. Copyright (C) 2000 Elsevier Science Ireland Ltd.

本文言語English
ページ(範囲)59-63
ページ数5
ジャーナルCancer Letters
148
1
DOI
出版ステータスPublished - 01-01-2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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