PROGNOSTIC AND ETIOLOGIC RELEVANCE OF 8-HYDROXYGUANOSINE IN HUMAN BREAST CARCINOGENESIS

In order to estimate the level of oxidative damage and its role in bre ast cancer, the promutagenic oxidative lesion, 8-hydroxy-2'-deoxyguano sine (8-OHdG), was determined in DNA isolated from 75 human breast tis sue specimens and from normal and transformed human breast cell lines, utilising a newly developed solid-phase immunoslot blot assay. The am ount of 8-OHdG was found to be 0.25 +/- 0.03 pmol/mu g in normal breas t tissue from reduction mammoplasty, 0.98 +/- 0.174 pmol/mu g in benig n tumours and 2.44 +/- 0.49 pmol/mu g DNA in malignant breast tissue w ith invasive ductal carcinoma. The malignant tissue had a statisticall y 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 b reast cancer cells compared with normal breast epithelial cells. In ad dition, 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 form ation and oestrogen responsiveness. The extent of 8-OHdG adducts did n ot show a discernible correlation with either the age or the smoking s tatus of the patients. These results indicate that the accumulation of 8-OHdG in DNA has a predictive significance for breast cancer risk as sessment and is conceivably a major contributor in the development of breast neoplasia. Copyright (C) 1996 Elsevier Science Ltd.