Fennell, TR; MacNeela, JP; Turner, MJ; Swenberg, JA
Acrylonitrile (AN), a chemical widely used in the manufacture of fibers and plastics, is carcinogenic in rat brain, stomach and Zymbal's gland. Both AN and a mutagenic metabolite, cyanoethylene oxide (CEO), can react with proteins. Measurement of specific adducts formed by reaction of AN or CEO with hemoglobin could be used to monitor exposure and metabolism. Male Fischer 344 rats received (2,3- 14C] AN p.o. Globin was isolated from blood for quantitation of bound radioactivity and adduct analysis. Binding of 3.4, 16.1, 31.3, 90.5, 1180, and 3670 nmol equivalents/g globin were found at doses of 0.1, 0.5, 1, 4, 10 and 28 mg/kg, respectively, indicating a non-linear dose response. Male B6C3F1 mice were treated similarly, and levels of 0.16, 3.4, and 92.8 nmol equivalents/g globin were found at doses of 0.1, 1, and 10 mg/kg, respectively, again indicating a non-linear dose response, and lower levels of binding than in rat. On chromatography of acid hydrolysed rat globin (4 mg AN/kg) using Dowex 50, seven radioactive peaks were found. The major peak comigrated with S-(2-carboxyethyl)cysteine (CEC). Reaction of rat or mouse globin in vitro with AN yielded CEC alone, but the extent of adduct formation was 5 fold lower in mouse globin than rat globin. CEC was derived from S-(2-cyanoethyl)cysteine formed by Michael addition of cysteine residues in hemoglobin to AN. CEC measurement could be used to monitor exposure to AN, and the other adducts, which are probably derived from AN metabolites, could be used as an indicator of metabolism.
General Biology-Symposia; Cytology and Cytochemistry-Animal; Biochemical Studies-General; Biochemical Studies-Proteins; Biochemical Studies-Porphyrins and Bile Pigments; Metabolism-General Metabolism; Metabolism-Proteins; Metabolism-Porphyrins and Bile Pigments; Blood; Toxicology-General; Neoplasms and Neoplastic Agents-Biochemistry; Neoplasms and Neoplastic Agents-Carcinogens and Carcinogenesis; Muridae
