Induction of gamma-glutamyl transpeptidase positive foci in rat liver by pyrolysis products of amino acids.
The activities of pyrolysis products for initiating or promoting preneoplastic lesions were tested. In experimental series I, N-2-fluorenylacetamide (2-FAA) was used as an initiator or a promoter and 3-amino-1,4-dimethyl-5H-pyrido-[4, 3-b] indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido [4, 3-b] indole (Try-P-2), 2-amino-6-methyldipyrido [1,2-a:3', 2'-d] imidazole (Glu-P-1) or 2-amino-dipyrido [1, 2-a:3', 2'] imidazole (Glu-P-2) was administered at a fixed dose and for the same period in the initiation stage or the promotion stage. Animals were subjected to partial hepatectomy or treated with carbon tetrachloride (CCl4) to increase the induction of gamma-glutamyl transpeptidase (gamma-GT) positive foci. Trp-P-1 and Glu-P-2 administered in either the initiation or promotion stage significantly increased the induction of gamma-GT positive foci (p less than 0.001). Glu-P-1 increased the induction of gamma-GT positive foci (P less than 0.001) when administered in the initiation stage but it was not effective when administered during the promotion stage. In experimental series II, animals were given a single dose of these chemicals at one of three different dose levels with partial hepatectomy and then were fed with 2-FAA and given a single dose of CCl4. Trp-P-1, Glu-P-1 and Glu-P-2 caused dose-dependent inductions of gamma-GT positive foci.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D004790:Enzyme Induction; D007093:Imidazoles / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008115:Liver Regeneration; D008297:Male; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis*
D002243:Carbolines; D007093:Imidazoles; D009153:Mutagens; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; C023847:Glu-P-2