Mutation Research 516 (2002) 101–111 Hemoglobin adducts and micronucleus frequencies in mouse and rat after acrylamide or N-methylolacrylamide treatment Birgit Paulsson a , Jan Grawé b,1 , Margareta Törnqvist a,∗ a Department of Environmental Chemistry, Stockholm University, S-106 91 Stockholm, Sweden b Department of Genetic and Cellular Toxicology, Stockholm University, S-106 91 Stockholm, Sweden Received 18 July 2001; received in revised form 28 January 2002; accepted 4 February 2002 Abstract 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. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Acrylamide; N-Methylolacrylamide; Glycidamide; Hemoglobin adducts; Micronuclei; Micronucleus test 1. Introduction In 1997 an accidental leakageof acrylamides (AAs) from a tunnel construction occurred in the south of Sweden. More than 200 workers were ex- posed and the groundwater became contaminated, which led to fish death, poisoning of grazing cattle ∗ Corresponding author. Tel.: +46-8-16-37-69; fax: +46-8-15-25-61. E-mailaddress: margareta.tornqvist@mk.su.se (M. Törnqvist). 1 Presentaddress: The Cell AnalysisCoreFacility,Uppsala University, S-751 85 Uppsala, Sweden. and potential exposure of residents within the area. The grouting agent used was based on a mixture of AA and N-methylolacrylamide (MAA). Studiesof health effects of the exposure and preliminary risk assessments have been performed, using hemoglobin (Hb) adducts as a measure of the in vivo doses [1,2]. The present study was initiated for an improved risk assessment of exposure to the two AAs with special regard to cancer risks. AA and MAA are reactive vinylic monomers used, separately or together, in the synthesis of polyAA products, e.g. for grouting and soil stabilization. MAA 1383-5718/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII: S 1 3 8 3 - 5 7 1 8 ( 0 2 ) 0 0 0 2 7 - X