Carcinogenicity of deuterium-labeled 1,2-dimethylhydrazine in mice

Journal Article · Fri Apr 15 04:00:00 EDT 1988 · Cancer Res.; (United States)

OSTI ID:7225141

Turusov, V S; Lanko, N S; Parfenov, Y D; Gordon, W P; Nelson, S D; Hillery, P S; Keefer, L K

To study the effect of deuterium substitution on the carcinogenicity of 1,2-dimethylhydrazine (DMH) in mice, two comparisons were made between DMH and its fully methyl-deuterated analogue, (/sup 2/H6)DMH. In a lifetime study with the CBA strain, groups of 19-30 animals of each sex were dosed s.c. weekly with 8 mg/kg of either DMH or (/sup 2/H6)DMH for 8, 16, or 32 weeks. In the second study, female CF-1 mice were given DMH or (/sup 2/H6)DMH in 10 weekly s.c. doses of 12 mg/kg each (13.2 mg/kg for (/sup 2/H6)DMH) and examined for colon tumors 36 weeks after the first dose. Deuteration significantly decreased tumor incidence in the colon of males (P less than 0.01) and the anal tissue of both sexes (P less than 0.05) but increased that of hepatomas and lung tumors in males (P less than 0.01). Substrate deuteration did not significantly affect overall incidence of any other tumor type, however, including hemangioendotheliomas and kidney tumors in both sexes, as well as colon, uterine, ovarian, liver, and lung tumors in females. The results indicate that C--H bond breakage is kinetically important in the activation of DMH to its ultimately carcinogenic form in organs such as the male colon (relative risk in DMH-versus (/sup 2/H6)DMH-treated animals approximately equal to 6), and that inhibition of this process by substrate deuteration allows a diversionary mechanism having a smaller isotope effect to become relatively more extensive. The qualitatively different effect in other organs (e.g., kidney, relative risk approximately equal to 1) supports recent suggestions that the net mechanism of activation can differ from one target tissue to another, possibly by striking a different balance between parallel metabolic pathways.

• Research Organization: Cancer Research Centre, Moscow (USSR)
• OSTI ID: 7225141
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 48:8; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BODY
CARCINOGENESIS
CARCINOGENS
DEUTERIUM
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENTAL NEOPLASMS
FEMALE GENITALS
GASTROINTESTINAL TRACT
GONADS
HEPATOMAS
HYDRAZINE
HYDROGEN ISOTOPES
INTESTINES
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPES
KIDNEYS
LARGE INTESTINE
LIGHT NUCLEI
LUNGS
MAMMALS
MICE
NEOPLASMS
NITROGEN COMPOUNDS
NUCLEI
ODD-ODD NUCLEI
ORGANS
OVARIES
PATHOGENESIS
RESPIRATORY SYSTEM
RODENTS
SEX DEPENDENCE
STABLE ISOTOPES
TRACER TECHNIQUES
UTERUS
VERTEBRATES