GROWTH-INHIBITION AND DNA DAMAGE INDUCED BY BENZO[A]PYRENE AND FORMALDEHYDE IN PRIMARY CULTURES OF RAT TRACHEAL EPITHELIAL-CELLS
GROWTH-INHIBITION AND DNA DAMAGE INDUCED BY BENZO[A]PYRENE AND FORMALDEHYDE IN PRIMARY CULTURES OF RAT TRACHEAL EPITHELIAL-CELLS
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DOI：
10.1016/0027-5107(88)90122-4
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发表时间：
1988-09-01
期刊：
影响因子：
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通讯作者：
MARCHOK, AC
中科院分区：
文献类型：
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作者：
COSMA, GN;JAMASBI, R;MARCHOK, AC
本实验观察了苯并[a]芘（BAP）和甲醛（HCHO）单独及联合作用对大鼠气管上皮细胞生长和DNA损伤的影响。用25 μ M BAP处理24小时或用200 μ M HCHO处理90分钟的细胞培养物在细胞生长方面没有显著降低。然而，当培养物暴露于BAP，然后暴露于HCHO以及相反的顺序时，它们的组合处理使细胞生长减少了对照的60%。这些处理都没有显着降低细胞活力判断染料排斥，也没有提高细胞终末分化所测量的皮质包膜形成。DNA损伤的碱性洗脱分析检测到作为HCHO处理的结果的DNA-蛋白质交联（DPC）和DNA单链断裂（SSB），而BAP处理仅引起SSB。HCHO诱导的SSB在2 h内修复，而BAP诱导的SSB在处理后3天检测到。用BAP然后用HCHO组合处理细胞培养物导致比单独从任一试剂获得更多的SSB，但比单独从HCHO检测到的DPC少。从这种联合治疗中获得的SSB数量增加可能与早期体内-体外研究中观察到的致癌作用显著增强有关。
The effects of benzo[a]pyrene (BAP) and formaldehyde (HCHO), alone and combined, on cell growth and DNA damage were determined in primary cultures of rat tracheal epithelial cells dissociated from rat tracheas. Cell cultures treated with 25 .mu.M BAP for 24 h or 200 .mu.M HCHO for 90 min did not have a marked reduction in cell growth. However, their combined treatment reduced cell growth by 60% of control when cultures were exposed to BAP followed by HCHO as well as the reverse order. None of these treatments significantly decreased cell viability as judged by dye exclusion, nor did they enhance cell terminal differentiation as measured by cornified envelope formation. Alkaline elution analysis of DNA damage detected both DNA-protein crosslinks (DPC) and DNA single-strand breaks (SSB) as a result of HCHO treatment, whereas BAP treatment caused only SSB. While HCHO-induced SSB were repaired within 2 h, BAP-induced SSB were detected 3 days after treatment. Combined treatment of cell cultures with BAP followed by HCHO resulted in more SSB than was obtained from either agent alone, but less DPC than was detected from HCHO alone. The increased number of SSB obtained from this combined treatment may be related to the marked enhancement of carcinogenesis observed in earlier in vivo-in vitro studies.