Prognostic and aetiological relevance of 8-hydroxyguanosine in human breast carcinogenesis.
In order to estimate the level of oxidative damage and its role in breast cancer, the promutagenic oxidative lesion, 8-hydroxy-2'-deoxyguanosine (8-OHdG), was determined in DNA isolated from 75 human breast tissue specimens and from normal and transformed human breast cell lines, utilising a newly developed solid-phase immunoslot blot assay. The amount of 8-OHdG was found to be 0.25 +/- 0.03 pmol/microgram in normal breast tissue from reduction mammoplasty, 0.98 +/- 0.174 pmol/microgram in benign tumours and 2.44 +/- 0.49 pmol/microgram DNA in malignant breast tissue with invasive ductal carcinoma. The malignant tissue had a statistically significant 9.76-fold higher level of 8-OHdG than normal tissue (P < 0.001, Mann-Whitney). A statistically significant 12.9-fold (P = 0.004) higher endogenous formation of 8-OHdG was also observed in cultured breast cancer cells compared with normal breast epithelial cells. In addition, a significantly elevated level (3.35-fold higher, P < 0.05) of 8-OHdG observed in oestrogen receptor-positive compared with oestrogen-negative malignant tissues, and in breast cancer cell lines (9.3-fold higher, P = 0.007) suggests a positive relationship between 8-OHdG formation and oestrogen responsiveness. The extent of 8-OHdG adducts did not show a discernible correlation with either the age or the smoking status of the patients. These results indicate that the accumulation of 8-OHdG in DNA has a predictive significance for breast cancer risk assessment and is conceivably a major contributor in the development of breast neoplasia.
Musarrat
J
J
Department of Radiology, Ohio State University, Columbus 43210, USA.
Arezina-Wilson
J
J
Wani
A A
AA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry* / Q000209:etiology / Q000235:genetics; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D012907:Smoking / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine