skip to main content

Title: DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion

Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of (/sup 14/C)N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.
Authors:
; ;
Publication Date:
OSTI Identifier:
5991610
Resource Type:
Journal Article
Resource Relation:
Journal Name: JNCI, J. Natl. Cancer Inst.; (United States); Journal Volume: 70:1
Research Org:
Institute of Pathology, University of Munich, Federal Republic of Germany
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; DNA; ALKYLATION; LIVER; CARCINOGENESIS; NITROSAMINES; BIOLOGICAL EFFECTS; BIOLOGICAL PATHWAYS; CARBON 14 COMPOUNDS; CARCINOMAS; CELL CYCLE; INTRAVENOUS INJECTION; PATHOLOGY; RATS; TRACER TECHNIQUES; AMINES; ANIMALS; BODY; CHEMICAL REACTIONS; DIGESTIVE SYSTEM; DISEASES; GLANDS; INJECTION; INTAKE; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; NEOPLASMS; NITROSO COMPOUNDS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PATHOGENESIS; RODENTS; VERTEBRATES 560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987); 550201 -- Biochemistry-- Tracer Techniques