title: Nonclonal growth of preneoplastic cells positive for glutathione S-transferase P-form in the rat liver.
abstract: We investigated the process of induction of preneoplastic cells positive for glutathione S-transferase P-form (GST-P) in the rat liver. AAF (2-Acetylaminofluorene) mixed with normal rat chow at high concentration (0.04%) induced 517 000 ± 86,000 GST-P(+) single hepatocytes/g liver after 2 weeks followed by induction of a few foci and nodules after 4-6 weeks. Overproduction of GST-P(+) single hepatocytes was dose- and time-dependent, and the induction kinetics were typical of first-order consecutive reaction, by which induction of the positive cells was nongenetic. Quantitative analysis indicated that the estimated numbers of cells in foci and nodules at 4-6 weeks after exposure to AAF ranged from 2.7 × 10(4) (2(14.7)) to 3.6 × 10(6) (2(21.7)) cells, and 2.0 × 10(4) (2(14.3)) to 2.7 × 10(6) (2(21.4)) cells, respectively, when analyzed by using two equations. According to the initiated cell theory of Farber, foci and nodules are formed through sequential cell division of 14 to 21-times or more within a short time period. The rapid growth exceeded the rate of cell division, indicating that the growth of preneoplastic cells is based on a nonclonal penetration mechanism.
authors.affiliation: Department of Biomedical Sciences, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Japan. k-satoh@well.ac.jp
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Satoh
authors.forename: Daishi
authors.initials: D
authors.lastname: Yamakawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kasai
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayakari
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.forename: Tomisato
authors.initials: T
authors.lastname: Miura
mesh_terms: D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002471:Cell Transformation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase