Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene (GSTP1), appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to carcinogens. Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to augment expression of several carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies. Another major interest pursued in the laboratory is the elucidation of mechanisms of sensitivity and resistance exhibited by prostate cancer cells treated with topoisomerase-targeted antineoplastic drugs. These studies focus on analysis of mutant topoisomerase target species, on the contribution of known biochemical determinants of drug resistance to prostate cancer chemotherapy treatment failure in vivo, and on discovery of new gene products that mediate drug resistance in prostatic carcinoma cells.