Carcinogenicity of single doses of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in Syrian golden hamsters and the persistence of alkylated purines in the DNA of various tissues
The carcinogenicity of N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) has been determined in adult male Syrian golden hamsters following a single i.p. injection or two-thirds of the acute 50% lethal dose, or 30 and 60 mg/kg, respectively. The principal site of action of these agents was the forestomach, squamous cell papillomas of this organ developing in 53 and 61% of the animals receiving the higher doses of NMU and N-nitroso-N-ethylurea, respectively. NMU also induced a low incidence of liver tumors (17%). Very few tumors were seen at other sites. The formation and removal of alkylated purines in DNA was measured in various tissues up to 50 hr after administration of (/sup 14/C)NMU. Methylation products were detected in all tissues examined, the level in liver being somewhat higher than in other tissues. The removal of 7-methylguanine and 3-methyladenine from DNA occurred at approximately similar rates in all tissues examined, indicating no substantial differences in N-glycosylase activities. Removal of the promutagenic DNA lesion O6-methylguanine varied considerably from tissue to tissue; very little occurred in brain or kidney, while up to 36 and 32% were lost from DNA of intestine and testes, respectively. In the liver, there were relatively small changes in O6-methylguanine levels up to 24 hr; but by 50 hr, 38% had been removed. The persistence of O6-methylguanine relative to 7-methylguanine was highest in the DNA of the brain and intestine and lowest in that of the liver. These results indicate that in this experimental system, the formation and persistence of O6-methylguanine in DNA is insufficient alone to account for the organotropic effect of NMU.
- Research Organization:
- International Agency for Research on Cancer, Lyon, France
- OSTI ID:
- 6143781
- Journal Information:
- Cancer Res.; (United States), Vol. 43:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
NITROSO COMPOUNDS
METABOLISM
TOXICITY
CARBON 14 COMPOUNDS
CARCINOGENESIS
DNA
HAMSTERS
LIVER
METABOLITES
SENSITIVITY
STOMACH
TRACER TECHNIQUES
TUMOR CELLS
ANIMAL CELLS
ANIMALS
BODY
DIGESTIVE SYSTEM
GASTROINTESTINAL TRACT
GLANDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550201 - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques