Induction of micronuclei in mouse and rat by glycidamide, genotoxic metabolite of acrylamide.
Male CBA mice and male Sprague-Dawley rats were treated by i.p. injection of glycidamide (GA), the presumed genotoxic metabolite of acrylamide (AA). GA was obtained through a new way of synthesis. As an endpoint of chromosome damage, micronucleus (MN) induction in erythrocytes was measured. Hemoglobin (Hb) adducts were used as a measure of in vivo dose of GA. GA induced linear dose-dependent increases in adduct levels in both species. Rats exhibit, compared with mice, 30% higher Hb adduct levels per unit of administered amount of GA. The incremental MN frequencies per administered dose of GA in mice showed a linear-quadratic dose-dependent curve. In the rat no positive dose-response relationship was obtained, probably due to toxic effects to the bone marrow. The main result of this study is the finding that after treatment with synthetic GA the MN frequency per unit of the in vivo dose of GA in the mouse is very similar to that obtained in a previous study, where animals were treated with AA and GA as a metabolite. This equality in potency of GA, whether its in vivo dose is established by injection of synthetic GA or through metabolism of AA, supports the view that GA is the predominant genotoxic factor in AA exposure.
Paulsson
Birgit
B
Department of Environmental Chemistry, Stockholm University, S-10691 Stockholm, Sweden.
Kotova
Natalia
N
Grawé
Jan
J
Henderson
Alistair
A
Granath
Fredrik
F
Golding
Bernard
B
Törnqvist
Margareta
M
D020106:Acrylamide / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006454:Hemoglobins / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004852:Epoxy Compounds; D006454:Hemoglobins; D009153:Mutagens; D020106:Acrylamide; C071834:glycidamide