The formation of
DNA adducts can lead to DNA replication errors and the potential for
carcinogenesis.
DNA adducts have been detected in prostate cells, but the distribution of adducts with respect to
prostate cancer risk factors and histology is unknown. In a study of 130 Caucasian (n = 61) and African-American (n = 69) men with
prostate cancer who underwent radical
prostatectomy, we quantified
polycyclic aromatic hydrocarbon (PAH)-
DNA adducts in prostate
tumor and adjacent nontumor cells by immunohistochemistry. A strong correlation between paired adduct levels in the two cell types was observed (r = 0.56; P < 0.0001); however, nontumor cells had a significantly higher level of adducts compared with
tumor (0.30 absorbance units +/- 0.05 versus 0.17 absorbance units +/- 0.04; P < 0.0001). Variables significantly associated with
PAH-DNA adduct levels in
tumor cells included primary Gleason grade,
tumor volume, and log-transformed
prostate-specific antigen (PSA) at time of diagnosis.
Tumors with a primary Gleason grade of 5 had significantly lower
PAH-DNA adduct levels than
tumor cells with a primary Gleason grade of 3 or 4 (P < 0.0001 for both).
Tumors that involved 10% or less of the prostate gland had significantly higher
PAH-DNA adduct levels than
tumors that involved 15 to 20% of the prostate gland (P = 0.004). PSA levels were inversely associated with
PAH-DNA adduct levels in
tumor cells (P = 0.009). A similar, albeit less significant, inverse association was observed between PSA and
PAH-DNA adduct levels in nontumor cells (P = 0.07). Interestingly, increasing primary Gleason grade was associated with increasing
PAH-DNA adduct levels in adjacent nontumor cells (P = 0.008). Our results show that PAH-
DNA adducts are present in the prostate but vary with regard to cellular histology. In prostate
tumor cells, decreased cellular differentiation and increased
tumor proliferation may reduce
PAH-DNA adduct levels.