Carcinogenic potential of benzene and toluene when evaluated using cyclin-dependent kinase activation and p53-DNA binding.
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.
Dees
C
C
Risk Analysis Section, Oak Ridge National Laboratory, Tennessee, USA.
Askari
M
M
Henley
D
D
D000818:Animals; D001483:Base Sequence; D001554:Benzene / Q000633:toxicity*; D001665:Binding Sites / Q000235:genetics; D042846:CDC2-CDC28 Kinases; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004247:DNA / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D014050:Toluene / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D014050:Toluene; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D001554:Benzene