Polycyclic aromatic hydrocarbon-DNA adducts in prostate cancer
Polycyclic aromatic hydrocarbon-DNA adducts in prostate cancer
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DOI：
10.1158/0008-5472.can-04-2323
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发表时间：
2004-12-15
期刊：
影响因子：
11.2
通讯作者：
Tang, DL
中科院分区：
文献类型：
--
作者：
Rybicki, BA;Rundle, A;Tang, DL
DNA加合物的形成可能导致DNA复制错误和致癌的可能性。DNA加合物已在前列腺细胞中被检测到，但与前列腺癌危险因素和组织学相关的加合物的分布尚不清楚。在对130名高加索人的研究中。采用免疫组织化学方法对61例前列腺癌患者和69例非裔美国人前列腺癌根治术患者的前列腺癌及癌旁组织中多环芳烃(PAH)-DNA加合物进行定量研究。两种细胞之间的加合物水平之间有很强的相关性(r=0.56P<；0.0001)，但非肿瘤细胞的加合物水平明显高于肿瘤细胞(0.30Unit0.05vs.0.17吸光度单位0.04；P<；0.0001)。与肿瘤细胞中PAH-DNA加合物水平显著相关的变量包括原发Gleason分级、肿瘤体积和诊断时的对数转化的前列腺特异性抗原(PSA)。原发Gleason分级为5级的肿瘤细胞的PAH-DNA加合物水平显著低于原发Gleason分级为3或4级的肿瘤细胞(P<；两者均为0.0001)。肿瘤累及10%或更少的前列腺癌，其多环芳烃-DNA加合物水平显著高于累及15%至20%的前列腺癌(P=0.004)。PSA水平与肿瘤细胞中多环芳烃-DNA加合物水平呈负相关(P=0.009)。在非肿瘤细胞中，PSA和PAH-DNA加合物水平之间也观察到了类似的，尽管不那么显著的负相关(P=0.07)。有趣的是，原发Gleason分级的增加与邻近非肿瘤细胞中多环芳烃-DNA加合物水平的增加有关(P=0.008)。我们的结果表明，PAH-DNA加合物存在于前列腺中，但在细胞组织学方面有所不同。在前列腺肿瘤细胞中，细胞分化减少和肿瘤增殖增加可能会降低PAH-DNA加合物的水平。
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.