Dees C, Askari M, Henley D
Risk Analysis Section, Oak Ridge National Laboratory, Tennessee, USA.
Environ Health Perspect. 1996 Dec;104 Suppl 6(Suppl 6):1289-92. doi: 10.1289/ehp.961041289.
Benzene is carcinogenic, whereas toluene is thought to have little carcinogenic potential. Benzene and toluene were found to activate cyclin-dependent kinase 2 in rat liver epithelial (RLE) and HL60 cells. pRb105 was hyperphosphorylated in RLE cells treated with either solvent. Kinase activation and subsequent hyperphosphorylation of pRb105 and p53 by benzene or toluene may be responsible for their growth promotional effects, but it does not account for increased potential of benzene to induce cancer. Therefore, we examined the ability of these solvents to increase p53-DNA site-specific binding in RLE cells. Benzene increased p53-DNA site-specific DNA binding in RLE cells compared to control levels or the effects of toluene. Increased p53-DNA site-specific binding by benzene may be caused by damage to cellular DNA. If so, although both solvents appear to have promotional activity, the increased potential of benzene to damage DNA may be responsible to the difference in the ability of benzene to cause cancer.
苯具有致癌性，而甲苯被认为几乎没有致癌潜力。在大鼠肝上皮（RLE）细胞和HL60细胞中发现，苯和甲苯可激活细胞周期蛋白依赖性激酶2。在用任一种溶剂处理的RLE细胞中，pRb105发生了过度磷酸化。苯或甲苯引起的激酶激活以及随后pRb105和p53的过度磷酸化可能是其促进生长作用的原因，但这并不能解释苯诱导癌症的潜在可能性增加。因此，我们研究了这些溶剂增加RLE细胞中p53-DNA位点特异性结合的能力。与对照水平或甲苯的作用相比，苯增加了RLE细胞中p53-DNA位点特异性DNA结合。苯导致的p53-DNA位点特异性结合增加可能是由细胞DNA损伤引起的。如果是这样，尽管两种溶剂似乎都具有促进活性，但苯破坏DNA的潜在可能性增加可能是导致苯致癌能力差异的原因。
