Induction of 1,N(2)-etheno-2'-deoxyguanosine in DNA exposed to beta-carotene oxidation products.
Epidemiological studies testing the effect of beta-carotene in humans have found a relative risk for lung cancer in smokers supplemented with beta-carotene. We investigated the reactions of retinal and beta-apo-8'-carotenal, two beta-carotene oxidation products, with 2'-deoxyguanosine to evaluate their DNA damaging potential. A known mutagenic adduct, 1,N(2)-etheno-2'-deoxyguanosine, was isolated and characterized on the basis of its spectroscopic features. After treatment of calf thymus DNA with beta-carotene or beta-carotene oxidation products, significantly increased levels of 1,N(2)-etheno-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine were quantified in DNA. These lesions are believed to be important in the development of human cancers. The results reported here may contribute toward an understanding of the biological effects of beta-carotene oxidation products.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26.077, CEP 05599-970 São Paulo, Brazil.
Sabrina A
SA
Marques
Ana Paula M
AP
Loureiro
Osmar F
OF
Gomes
Camila C M
CC
Garcia
Paolo
P
Di Mascio
Marisa H G
MH
Medeiros
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002338:Carotenoids / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000302:isolation & purification; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012172:Retinaldehyde / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019207:beta Carotene / Q000378:metabolism*
D000975:Antioxidants; D018736:DNA Adducts; C110652:beta-apo-8'-carotenal; D019207:beta Carotene; D002338:Carotenoids; D004247:DNA; C427203:calf thymus DNA; D003849:Deoxyguanosine; D012172:Retinaldehyde