Hemoglobin adducts and micronucleus frequencies in mouse and rat after acrylamide or N-methylolacrylamide treatment.
The reactive industrial chemicals acrylamide (AA) and N-methylolacrylamide (MAA) are neurotoxic and carcinogenic in animals, MAA showing a lower potency than AA. The causative agent in AA-induced carcinogenesis is assumed to be the epoxy metabolite, glycidamide (GA), which in contrast to AA gives rise to stable adducts to DNA. The causative agent in MAA induced carcinogenesis is so far not studied. The two AAs were studied in mice and rats using analysis of hemoglobin (Hb) adducts as a measure of in vivo doses and the in vivo micronucleus (MN) assay as an end-point for chromosome damage. Male CBA mice were treated by intraperitoneal (i.p.) injection of three different doses and male Sprague-Dawley rats with one dose of each AA. Identical adducts were monitored from the two AAs [N-(2-carbamoylethyl)valine] and the respective epoxide metabolites [N-(2-carbamoyl-2-hydroxyethyl)valine]. Per unit of administered amount, AA gives rise to higher (three to six times) Hb adduct levels than MAA in mice and rats. Mice exhibit, compared with rats, higher in vivo doses of the epoxy metabolites, indicating that AAs were more efficiently metabolized in the mice. In mouse the two AAs induced dose-dependent increases in both Hb adduct level and MN frequency in peripheral erythrocytes. Per unit of administered dose MAA showed only half the potency for inducing micronuclei compared with AA, although the MN frequency per unit of in vivo dose of measured epoxy metabolite was three times higher for MAA than for AA. No increase in MN frequency was observed in rat bone marrow erythrocytes, after treatment with either AA. This is compatible with a lower sensitivity of the rat than of the mouse to the carcinogenic action of these compounds.
Paulsson
Birgit
B
Department of Environmental Chemistry, Stockholm University, S-106 91, Sweden.
Grawé
Jan
J
Törnqvist
Margareta
M
D020106:Acrylamide / Q000633:toxicity*; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D051381:Rats; D017207:Rats, Sprague-Dawley
D000178:Acrylamides; D002273:Carcinogens; D018736:DNA Adducts; D006454:Hemoglobins; D020106:Acrylamide; D004247:DNA; C066443:N-methylolacrylamide