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

Journal Article · Sat Jan 01 00:00:00 EST 1983 · JNCI, J. Natl. Cancer Inst.; (United States)

OSTI ID:5991610

Rabes, H M; Kerler, R; Wilhelm, R

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.

• Research Organization: Institute of Pathology, University of Munich, Federal Republic of Germany
• OSTI ID: 5991610
• Journal Information: JNCI, J. Natl. Cancer Inst.; (United States), Vol. 70:1
• Country of Publication: United States
• Language: English

Related Subjects

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