Study on the mutagenicity and antimutagenicity of beta-ionone in the Salmonella/microsome assay.
beta-Ionone (BIO) is a degraded (C(13)) sesquiterpenoid compound found in a variety of edible and aromatic plants. BIO and other ionone derivatives have been used in fragrance products and as flavoring food additives. In this study we investigated the mutagenic and antimutagenic activities of BIO using the Salmonella/microsome assay. Mutagenicity was evaluated by two tests with Salmonella typhimurium strains TA100, TA98, TA97a and TA1535, without and with addition of S9 mixture. A first assay was performed by the plate incorporation procedure and a confirmation test by the pre-incubation method. In either test, no increase in the number of his(+) revertant colonies over the negative (solvent) control values was noted with any of the four tester strains thereby indicating that BIO was not genotoxic in the Salmonella assay. Antimutagenic activity was investigated by testing (by the plate incorporation method) different non-toxic doses of BIO against one or more non-toxic doses of direct-acting (sodium azide: SA, 4-nitroquinoline-N-oxide: 4-NQNO, 2-nitrofluorene: 2-NF and nitro-o-phenylenediamine: NPD) as well as indirect-acting (cyclophosphamide: CP, benzo[a]pyrene: B[a]P, aflatoxin B1: AFB1, 2-aminoanthracene: 2-AA, and 2-aminofluorene: 2-AF) mutagens. BIO did not alter the effects of any direct-acting mutagen or B[a]P and 2-AF. Mutagenic effects of AFB1 and CP, however, were markedly and dose-dependently antagonized by BIO. It has been reported that, in the rat liver, activation of B[a]P and 2-AF depend on CYP1A1 activity, and that CYP2B subfamily is involved in the metabolic activation of CP and AFB1. It has also been described that BIO is a potent inhibitor of CYP2B1/2 and a weaker inhibitor of CYP1A1. Therefore, antagonism of CP-and AFB1-induced mutagenic effects by BIO could have been mediated-at least in part-by the inhibition of CYP2B enzymes.
Gomes-Carneiro
M R
MR
Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
Dias
Daniela M M
DM
Paumgartten
Francisco J R
FJ
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005503:Food Additives; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009152:Mutagenicity Tests; D045792:Norisoprenoids / Q000494:pharmacology*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D016587:Antimutagenic Agents; D005503:Food Additives; D045792:Norisoprenoids; C008157:beta-ionone