O-6-ALKYLGUANINE DNA ALKYLTRANSFERASE ACTIVITY LEVELS IN NORMAL, BENIGN AND MALIGNANT HUMAN FEMALE BREAST

The enzyme O-6-alkylguanine DNA alkyltransferase (AGT) is implicated in the repair of DNA damage by chemotherapeutic chloroethylnitrosoureas (CNUs) and plays a vital role in determining the sensitivity of cancer cells to this class of compounds. We have measured the AGT activity in 41 human female breast tissues including normal, benign and malignant specimens. The patients with breast cancer in advanced stages have shown a statistically significant 2.37-fold (p=0.007) higher level of AGT activity compared to normal. An inter-individual variation of 1.8-fold in normal, 10.8-fold in benign and 7.6-fold in malignant tissues was observed. The average number of methyl group acceptor molecules per cell were estimated to be 19,053 +/- 903, 20,227 +/- 1,806 and 45,330 +/- 5,418 (SEM) in normal, benign and malignant tissue, respectively. These results for the first time emphasize the predictive role of AGT in selecting the responder patients by AGT determination in breast tumor biopsies and further encourage terapeutic trials based on biochemical modulation of CNU resistance against malignant cells. (C) 1995 Academic Press, Inc.