6533b820fe1ef96bd1279c49

RESEARCH PRODUCT

Intra- and extra-cellular DNA damage by harmine and 9-methyl-harmine

Rosa Erra-balsellsMariana VignoniBernd EpeFranco M. Cabrerizo

subject

Guanineb-carbolinesUltraviolet RaysDNA damageBiophysicsFree radical damage to DNACHO CellsMicronucleiBiologyPhototoxicitychemistry.chemical_compoundCricetulusHarmineCyclobutane pyrimidine photodimersCricetinaeAnimalsRadiology Nuclear Medicine and imagingPurine metabolismRadiationRadiological and Ultrasound TechnologyCell growthOtras Ciencias QuímicasCiencias QuímicasDNAHydrogen-Ion ConcentrationHarmineQuímica OrgánicaBiochemistrychemistryMicronucleus testBiophysicsPhotosensitizationPhototoxicityCIENCIAS NATURALES Y EXACTASDNADNA Damage

description

It is known that b-carbolines are able to produce photosensitized damage in cell-free DNA, but there is little information on their effects on cellular DNA. Therefore, we have analyzed the DNA damage produced by harmine and 9-methyl-harmine under UVA irradiation in V79 cells, together with the associated generation of micronuclei and photocytotoxicity. The results indicate that the most frequent photoproducts generated in the cellular DNA are modified purines such as 8-oxo-7,8-dihydroguanine. Only relatively few single-strand breaks were observed. CPDs were absent, although they were generated in cell-free DNA irradiated under the same conditions. The overall extent of DNA damage in the cells was considerably smaller than the one observed in cell free DNA. The generation of cellular DNA damage was associated with a significant generation of micronuclei and decreased cell proliferation. The data indicate that b-carbolines act as photosensitizers in mammalian cells. The spectrum of DNA modification, and therefore the mechanism of DNA damage generation, differs considerably from that observed with cell-free DNA. Fil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Erra Balsells, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina Fil: Epe, Bernd. University of Mainz; Alemania Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina

yearjournalcountryeditionlanguage
2014-02-13Journal of Photochemistry and Photobiology B: Biology
https://doi.org/10.1016/j.jphotobiol.2014.01.020