Dose-response studies with nitrosoheptamethyleneimine and its alpha-deuterium-labeled derivative in F344 rats

Journal Article · Mon Nov 01 04:00:00 EST 1982 · JNCI, J. Natl. Cancer Inst.; (United States)

OSTI ID:6620335

Lijinsky, W; Reuber, M D; Davies, T S; Riggs, C W

A dose-response study of the carcinogenicity of nitrosoheptamethyleneimine (N-HEP) in inbred F344 male and female rats was performed by administration of the nitrosamine at several concentrations in drinking water to groups of 20 rats. The concentrations differed by a factor of nearly 2.5 and ranged from 1.0 to 100 mg/liter. The duration of treatment was 13, 25, 50, or 100 weeks, after which the animals were allowed to die naturally of tumors induced. In most treated groups the incidence of tumors of the upper gastrointestinal tract approached 100%. However, at the higher doses there was an inverse relationship between total dose and survival time of the rats. Matched treatment of groups of rat with N-HEP labeled with deuterium in the alpha positions resulted in longer survival. The slower action of the deuterium-labeled compound, as measured by a lower rate of death from tumors, suggests that cleavage of a carbon-hydrogen bond at an alpha position is a rate-limiting step in carcinogenesis by N-HEP in rats.

• Research Organization: Chemical Carcinogenesis Program, NCI-Frederick Cancer Research Facility, MD
• OSTI ID: 6620335
• Journal Information: JNCI, J. Natl. Cancer Inst.; (United States), Journal Name: JNCI, J. Natl. Cancer Inst.; (United States) Vol. 69:5; ISSN JJIND
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
BIOCHEMISTRY
BIOLOGICAL PATHWAYS
CARCINOGENESIS
CHEMISTRY
DEUTERIUM COMPOUNDS
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRINKING WATER
GASTROINTESTINAL TRACT
HYDROGEN COMPOUNDS
MAMMALS
NEOPLASMS
NITROSAMINES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN COMPOUNDS
PATHOGENESIS
RATS
RODENTS
TOXICITY
VERTEBRATES
WATER