title: Adenomatous polyposis coli influences micronuclei induction by PhIP and acrylamide in mouse erythrocytes.
abstract: Micronucleus (MN) induction in erythrocytes of multiple intestinal neoplasia (Min) mice with heterozygous Apc mutation was measured after s.c. injections of acrylamide, glycidamide, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and colchicine, and compared with wild-type (wt) mice. Since Apc influences microtubule dynamics, we wanted to test whether Min-mice were more sensitive to the production of MN than wild-type mice. We also examined the effect of pre-treatment with cytosine beta-D-arabinofuranoside (Ara C) and hydroxyurea, which inhibit ligation of DNA strand breaks in the repair of DNA adducts. All compounds induced a significant increase in MN in both strains of mice with the following potencies: acrylamide<glycidamide<PhIP. No difference in the induction of MN was seen between Min-mice and wt-mice exposed to acrylamide, glycidamide or colchicine without pre-treatment. However, in Min-mice, PhIP treatment induced much less MN than in wt-mice, with about four- and six-fold increase in MN in Min-mice and wt-mice, respectively. A reduced ability to repair PhIP adducts may be the reason for the lower induction of MN in Min-mice. Treatment with Ara C and hydroxyurea, to increase sensitivity, gave more than a four-fold increase in MN, but strongly reduced proliferation. Pre-treatment with Ara C and hydroxyurea made the Min-mice slightly more sensitive to MN induction by glycidamide compared to wt-mice. We conclude that Min-mice are less sensitive than wt-mice to MN induction by PhIP that forms bulky DNA adducts, while Min-mice and wt-mice are equally sensitive to MN induction by acrylamide and glycidamide that form DNA base adducts.
authors.affiliation: Department of Food Toxicology, Norwegian Institute of Public Health, PO Box 4404, Nydalen, NO-0403 Oslo, Norway. trine.husoy@fhi.no
authors.forename: T
authors.initials: T
authors.lastname: Husøy
authors.forename: L
authors.initials: L
authors.lastname: Abramsson-Zetterberg
authors.forename: H B
authors.initials: HB
authors.lastname: Ølstørn
authors.forename: J E
authors.initials: JE
authors.lastname: Paulsen
authors.forename: J
authors.initials: J
authors.lastname: Alexander
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D011125:Adenomatous Polyposis Coli / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D003078:Colchicine / Q000633:toxicity; D003561:Cytarabine / Q000494:pharmacology; D018736:DNA Adducts / Q000378:metabolism; D004852:Epoxy Compounds / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006918:Hydroxyurea / Q000494:pharmacology; D007093:Imidazoles / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D018736:DNA Adducts; D004852:Epoxy Compounds; D007093:Imidazoles; D009153:Mutagens; D003561:Cytarabine; D020106:Acrylamide; C071834:glycidamide; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D003078:Colchicine; D006918:Hydroxyurea