Roy S K, Trivedi A H, Bakshi S R, Patel S J, Shukla P H, Bhatavdekar J M, Patel D D, Shah P M
Cell Biology Division, The Gujarat Cancer Society, Asarwa, Ahmedabad, India.
J Exp Clin Cancer Res. 2000 Jun;19(2):169-73.
In vitro mutagen susceptibility has been observed as a predictor of cancer risk. To evaluate susceptibility to mutagen, we have studied the response to in vitro bleomycin (BLM) treatment in cultured peripheral blood lymphocytes (PBL) of 9 breast cancer families (BCFs). Eleven breast cancer patients (BCPs) and 36 healthy blood relatives (HBRs) from BCFs were included in the study. Data were compared with 22 healthy control women. The frequencies of chromosomal aberrations were evaluated after exposure to BLM in the last five hours. Mean frequency of BLM-induced chromosomal aberrations per cell (CA) observed among BCPs was significantly higher as compared to their HBRs as well as control subjects. Moreover, mean BLM-induced CA/cell value observed for HBRs was also significantly higher than that of control subjects. In comparison to controls, it was observed that there was four times more cancer risk in BCPs (OR=4.148, 95% CI=5.83-687.46) and 2.5 times more cancer risk in HBRs (OR=2.67, 95% CI=5.31-39.25). Lymphocytes from 90% of BCPs and 69% of HBRs were found to be sensitive to BLM (using a cutoff value = controls group mean + 1 SD). Thus, lymphocytes of BCPs and their HBRs were more sensitive to BLM exposure as compared to controls. Our finding indicated inefficient DNA repair capacity in BCFs. The HBRs in BCFs, having increased BLM-sensitivity, may be at higher risk to develop a similar cancer.
体外诱变敏感性已被视为癌症风险的一个预测指标。为了评估对诱变剂的敏感性,我们研究了9个乳腺癌家族(BCF)培养的外周血淋巴细胞(PBL)对体外博来霉素(BLM)治疗的反应。该研究纳入了来自BCF的11名乳腺癌患者(BCP)和36名健康血亲(HBR)。数据与22名健康对照女性进行了比较。在暴露于BLM后的最后5小时评估染色体畸变频率。与她们的HBR以及对照受试者相比,BCP中观察到的每细胞BLM诱导的染色体畸变平均频率显著更高。此外,HBR中观察到的每细胞BLM诱导的染色体畸变值也显著高于对照受试者。与对照组相比,观察到BCP患癌风险高出四倍(OR = 4.148,95% CI = 5.83 - 687.46),HBR患癌风险高出2.5倍(OR = 2.67,95% CI = 5.31 - 39.25)。发现90%的BCP和69%的HBR的淋巴细胞对BLM敏感(使用临界值 = 对照组平均值 + 1个标准差)。因此,与对照组相比,BCP及其HBR的淋巴细胞对BLM暴露更敏感。我们的发现表明BCF中DNA修复能力低下。BCF中具有增强的BLM敏感性的HBR可能患类似癌症的风险更高。