Role of diethylnitrosamine, 2-acetylaminofluorene and partial hepatectomy in the expression of glutathione-S-transferase-P and gamma-glutamyltranspeptidase in the early steps of rat liver carcinogenesis.
Three factors involved in the Solt and Farber model of rat liver carcinogenesis were studied alone and in various combinations: diethylnitrosamine (DEN) initiating dose, 2-acetylaminofluorene (2-AAF) feeding and partial hepatectomy. The administration of DEN alone (200 mg/kg) was able to switch on glutathione-S-transferase, placental type (GST-P) expression 3 weeks later at a low level (85 U/micrograms protein) which was stable for 10 weeks in the absence of histopathological lesions. During the same time, gamma-glutamyl transpeptidase (GGT) activity presented 2 waves of increase. The feeding of 0.03% 2-AAF for 2 weeks appeared as a determinant factor in the expression of GST-P protein as well as GGT induction (15- and 7-fold versus DEN alone, respectively). The addition of partial hepatectomy enhanced again GST-P expression (1.5-fold) and GGT induction (2-fold). However, GST-P foci increased in size, not in number while GGT foci increased both in size and in number. These data indicated that 2-AAF was a crucial component of the selection procedure since partial hepatectomy alone, with or without DEN initiation was inefficient in promoting GST-P expression. Therefore, 2-AAF would be able to promote the growth of GST-P-positive cells initiated by DEN, a mechanism likely responsible for its tumor-promoting effect.
Ould Elhkim
M
M
Institut de Recherches, Scientifiques sur le Cancer, CNRS, Villejuif, France.
Decloître
F
F
Martin
M
M
Loridon-Rosa
B
B
Frayssinet
C
C
D015073:2-Acetylaminofluorene; D000818:Animals; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006498:Hepatectomy; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D010920:Placenta / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis*
D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase