8-hydroxy-2--deoxyguanosine and Hepatoblastoma

Antioxidative flavonoids, ubiquitously included in vegetables, fruits and teas, are expected to prevent degenerative diseases. It is unclear, however, whether flavonoids can enter the cellular nuclei and suppress the oxidative damage of DNA. Here, several flavonoids at the physiological concentration of 10 microM were dosed to 2.5x10(7) HepG2 cells. The nuclei were isolated and determined in the incorporated flavonoid levels, and simultaneously exposed to reactive oxygen generated from 25 mM of 2,2'-azobis(2-amidinopropane) dihydrochloride. Most of the tested flavonoids were incorporated into the cells in the range between 1000 and 1600 pmol/10(7) cells, and were in the nuclei at 250-450 pmol/10(7) cells at the maximum incorporation after 30min of cell incubation. In the cells, 23% of quercetin (3,5,7,3',4'-OH) and 8% of luteolin (5,7,3',4'-OH) were the original aglycone forms and the others were the methylated and gulucuronide/sulfate conjugates, while 72% of kaempferol (3,5,7,4'-OH) and 85% of apigenin (5,7,4'-OH) were aglycones and located in the nuclei at the similar ratio of metabolites. Quercetin and luteolin significantly suppressed the formation of 8-oxo-7,8-dihydrodeoxyguanosine by 25% and 15%, respectively, compared to those in 0-time incubated cells with the flavonoids. Under such conditions of low level and hydroxyl-masked in the nuclei, the limited flavonoids were bioavailable antioxidants to prevent genetic damage and they were B-ring catechols such as quercetin and luteolin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Biological Availability; Cell Line, Tumor; Deoxyguanosine; Dose-Response Relationship, Drug; Flavonoids; Hepatoblastoma; Humans; Liver Neoplasms

The authors have revealed a significant association between hepatoblastoma and low birth weight. This study was done to explore the evidence that liver cells were oxidatively damaged, based on the hypothesis that oxidative damage to DNA is involved in the development of hepatoblastoma in children of low birth weight.. Oxidative DNA damage in the liver was examined by immunohistochemically detecting the presence of a DNA repair product, 8-hydroxy-2'-deoxyguanosine (8-OHdG), in five patients with hepatoblastoma and 14 children with non-neoplastic disease.. Positive staining for 8-OHdG was observed in all five patients with hepatoblastoma. Distribution of 8-OHdG positivity was diffuse in the intralobular area in one patient and was restricted to the periportal area of the lobules in four patients. There was no apparent correlation between birth weight of the patients, histological findings in the liver, and the distribution of 8-OHdG positivity. In children with non-neoplastic disease, 8-OHdG was detected in nine of 14 patients, and 8-OHdG was positive in the intralobular area of the liver parenchyma except in one patient.. These results suggest that the cause of oxidative DNA damage in patients with hepatoblastoma may be different from the cause, extensive parenchymal damage to the liver, in children with non-neoplastic disease, but the 8-OHdG formation is not specific to hepatoblastoma patients of low birth weight. Further studies to elucidate the true reason for the high incidence of hepatoblastoma in children of low birth weight are necessary.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Case-Control Studies; Child, Preschool; Deoxyguanosine; DNA Damage; Female; Hepatoblastoma; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Liver; Liver Neoplasms; Male