Production of ethane by rats treated with the colon carcinogen, 1,2-dimethylhydrazine.
Ethane was exhaled by rats treated with the colon carcinogen, 1,2-dimethylhydrazine (DMH). At 1 hr, ethane production (mean +/- SD) was 0.2 +/- 0.2 nmol/kg (controls) and 5.2 +/- 1.3, 13.7 +/- 3.4, and 27.7 +/- 9.6, respectively, for DMH injections of 0.15 mmol/kg (20 mg/kg of the dihydrochloride salt), 0.45 mmol/kg, and 1.35 mmol/kg. Rates of ethane evolution tapered off after 2 hr, but persisted for up to 3 hr at the lower dose, and up to 5-6 hr at the higher dose. Although ethane is produced in vivo during lipid peroxidation, experiments with vitamin E, a potent lipid antioxidant, indicated that lipid peroxidation was unlikely to be the source of ethane in DMH-treated rats: pretreatment with vitamin E had no effect on ethane formation from DMH but did suppress ethane production from rats treated with carbon tetrachloride, an inducer of hepatic lipid peroxidation. When rats were injected with 1,2-diethylhydrazine in place of DMH, large amounts of ethane and ethylene were produced (9800 and 5600 nmol/kg/hr). The hydrocarbon gases exhaled by rats may arise from dimerization of methyl radicals (.CH3) generated during the metabolism of DMH, and from ethyl radicals (.CH2CH3) generated during the metabolism of 1,2-diethylhydrazine. Previously, it was shown that methane and ethane are formed from methyl radicals in vitro. Other investigators have observed formation of hydrocarbon gases during the in vitro metabolism of monoalkylhydrazines by microsomes, and ethyl radicals, derived from monoethylhydrazine, have been detected by electron spin-resonance spectroscopy. The results presented here suggest that in vivo metabolism of DMH may produce methyl radicals. Methyl radicals are capable of interacting with biomolecules. Their indiscriminate reaction with tissue constituents may be a contributory factor in DMH-induced carcinogenesis.
Kang
J O
JO
Medical Technology Program, University of Arizona, Tucson 85724.
Slater
G
G
Aufses
A H
AH
Cohen
G
G
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004127:Dimethylhydrazines / Q000494:pharmacology*; D004980:Ethane / Q000378:metabolism*; D005030:Ethylenes / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D008697:Methane / Q000378:metabolism; D008763:Methylhydrazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration
D002273:Carcinogens; D004127:Dimethylhydrazines; D005030:Ethylenes; D008763:Methylhydrazines; C036216:ethylene; D019813:1,2-Dimethylhydrazine; D004980:Ethane; D008697:Methane