c-Jun expression in single cells and preneoplastic foci induced by diethylnitrosamine in B6C3F1 mice: comparison with the expression of pi-class glutathione S-transferase.
Expression of the oncogene product c-Jun was examined and compared with that of class pi glutathione S-transferase (GST-II) during chemical hepatocarcinogenesis in female and male mice. A single i.p. injection of diethylnitrosamine (DEN) (10 mg/kg) was administered to B6C3F1 mice and livers were immunohistochemically investigated with anti-c-Jun and anti-GST-II antibodies at various time points thereafter. In females, almost all foci detected by hematoxylin and eosin staining were positive for c-Jun 3, 6, 9 and 11 months after the DEN administration. Seventy-one and 82% of c-Jun-positive foci at 9 and 11 months respectively, were also positive for GST-II, while this was the case for only 15% at 6 months. In males almost all foci were also positive for c-Jun at 3 and 6 months, but 23% of foci were negative at 9 months. Unlike the foci in females, 96 and 79% of those in males expressing c-Jun were negative for GST-II at 6 and 9 months respectively. Both GST-II expression in foci of females and its lack in those of males were highly correlated with c-Jun expression. Furthermore, single cells expressing c-Jun were also observed in both sexes at 3 months and thereafter, but not at 2 or 4 weeks. Alterations in the numbers of c-Jun-positive single cells, minifoci and foci followed sequentially revealed the number of such single cells to decrease, while foci increased, the sum being relatively constant. On the other hand, while a large number of GST-II-positive single cells were detected in female livers 2 and 4 weeks after the DEN administration, they markedly decreased thereafter, suggesting that the majority were unlikely to give rise to foci. Thus, c-Jun may be a better positive marker not only for preneoplastic foci, but also putative precursor single cells in both female and male mice and therefore be useful for analysis of hepatocarcinogenic processes.
Nakano
H
H
Second Department of Biochemistry, Hirosaki University School of Medicine, Japan.
Hatayama
I
I
Satoh
K
K
Suzuki
S
S
Sato
K
K
Tsuchida
S
S
D000818:Animals; D004052:Diethylnitrosamine; D005260:Female; D015870:Gene Expression; D016758:Genes, jun; D005982:Glutathione Transferase / Q000032:analysis*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000737:chemistry* / Q000201:enzymology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis* / Q000235:genetics
D007527:Isoenzymes; D016755:Proto-Oncogene Proteins c-jun; D004052:Diethylnitrosamine; D005982:Glutathione Transferase