title: Exclusive induction of G:C to A:T transitions by 3-azido-1,2-propanediol in yeast.
abstract: Sodium azide is a strong mutagen which has been successfully employed in mutation breeding of crop plants. In biological systems, it is metabolized to azidoalanine, but further bioactivation to a putative ultimate mutagen as well as the nature of the induced DNA modifications leading to mutations remain elusive. In this study, mutations induced in the CAN1 gene of yeast Saccharomyces cerevisiae by the representative mutagen 3-azido-1,2-propanediol (azidoglycerol, AZG) have been sequenced. Analysis of the forward mutation spectrum to canavanine resistance revealed that AZG induced nearly exclusively G:C to A:T transitions. AZG also induced reversions to tryptophan prototrophy by base-pair substitutions in a dose-dependent manner. This unusual mutational specificity may be shared by other organic azido compounds.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: gruz@nihs.go.jp.
authors.forename: Petr
authors.initials: P
authors.lastname: Grúz
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachiouji-shi, Tokyo 192-0392, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sassa
authors.affiliation: Division of Medical Nutrition, Faculty of Healthcare, Tokyo Healthcare University, 3-11-3 Setagaya, Setagaya-ku, Tokyo 154-8568, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Hosoda
authors.affiliation: Department of Health and Nutrition, College of Human Environmental Studies, Kanto Gakuin University, 1-50-1 Mutsuura-Higashi, Kanazawa-ku, Yokohama 236-8503, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamagishi
authors.affiliation: Division of Medical Nutrition, Faculty of Healthcare, Tokyo Healthcare University, 3-11-3 Setagaya, Setagaya-ku, Tokyo 154-8568, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Usui
authors.affiliation: Division of Medical Nutrition, Faculty of Healthcare, Tokyo Healthcare University, 3-11-3 Setagaya, Setagaya-ku, Tokyo 154-8568, Japan.
authors.forename: Masatomi
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D001386:Azides / Q000494:pharmacology*; D002172:Canavanine / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000235:genetics; D016296:Mutagenesis / Q000187:drug effects*; D009154:Mutation / Q000187:drug effects*; D011409:Propylene Glycols / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014364:Tryptophan / Q000494:pharmacology
chemical_list: D026923:Amino Acid Transport Systems, Basic; D001386:Azides; C502212:CAN1 protein, S cerevisiae; D011409:Propylene Glycols; D029701:Saccharomyces cerevisiae Proteins; D002172:Canavanine; C052086:azidoglycerol; D014364:Tryptophan
keywords: Azide; Mutagenesis; Yeast