title: Aneugenic effects of benzoxazinones in cultured human cells.
abstract: Benzoxazinones (BAs) are natural products that are present in Gramineae and represent part of the plant defence system against pests. In recent years, sprouts of maize, wheat and rye have been used for the production of dietary supplements. We have investigated the potential genotoxic activities of a diverse range of synthetic derivatives of the most abundant natural BA, namely DIBOA (2,4-dihydroxy-1,4-benzoxazin-3-one), proposed for use as a potential herbicide. We have tested 18 synthetic BAs for potential effects in cultured HeLa cells. We found significantly higher micronucleus (MN) induction over the background level, with the solvent DMSO used as an internal control. Concentration-dependent effects were found between 1nM and 20nM for all the synthetic compounds studied. Immunostaining with an anticentromere antibody showed that >80% of MN induced gave a centromere-positive signal. Similarly, fluorescence in situ hybridization (FISH) analysis with alphoid centromere probes showed a positive hybridization signal, indicating that all compounds analyzed are aneugenic. Chemical modification of the N in the heterocyclic aromatic amine served us to suggest a relationship between the structure and the aneugenic effects of the compounds analyzed. Our findings indicate that benzoxazinoids could be potential genotoxins for human cells.
authors.affiliation: Grupo de Alelopatía, Departamento de Química Orgánica, Facultad de Ciencias, 11510 Puerto Real, Cádiz, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Arroyo
authors.forename: Nuria
authors.initials: N
authors.lastname: Chinchilla
authors.forename: José M G
authors.initials: JM
authors.lastname: Molinillo
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Macias
authors.forename: Antonio
authors.initials: A
authors.lastname: Astola
authors.forename: Manuela
authors.initials: M
authors.lastname: Ortiz
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Valdivia
mesh_terms: D024422:Aneugens / Q000633:toxicity*; D048588:Benzoxazines / Q000633:toxicity*; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D013329:Structure-Activity Relationship
chemical_list: D024422:Aneugens; D048588:Benzoxazines