ROLE OF TOBACCO RELATED CHEMICAL CARCINOGENS AND OXYRADICALS IN HUMAN CANCER

我们和我们的合作者先前测量了p53突变， 在非肿瘤人类肝脏组织中的水平。 这些数据是一致的 p53突变负荷可能指示先前致癌物假说 暴露和识别癌症风险增加的个体。 我们 再次使用最敏感的基于RFLP/PCR的基因型突变 分析系统，迄今为止，测量突变负荷， p53基因的密码子247和248在非肿瘤结肠组织中， 患有结肠癌的供体，具有癌症倾向的状况，例如， 溃疡性结肠炎和正常供体。 我们检测到G：C到A：T 在那些非肿瘤样品中的转变，这些样品是从 其中肿瘤也具有G：C到A：T转变的供体。 这些 观察到转换，绝对突变高出数倍 正常献血者的对照样本的频率。 十分之七 溃疡性结肠炎样本显示绝对突变高出数倍， G：C到A：T转换的频率高于婴儿和正常成人。 这些初步的结果表明，非肿瘤性结肠组织中， 具有p53密码子248突变的癌症患者和具有 溃疡性结肠炎在密码子248处携带较高的p53突变负荷， 来自没有已知结肠疾病的非癌症供体的那些。

We and our collaborators have previously measured the p53 mutation level in nontumorous human liver tissue. The data are consistent with the hypothesis that p53 mutation load may indicate previous carcinogen exposure and identify individuals at increased cancer risk. We are again using the most sensitive, RFLP/PCR based, genotypic mutation analysis system available thus far, to measure the mutation load at codons 247 and 248 of the p53 gene in nontumorous colon tissue from donors with colon cancer, with cancer prone conditions, e.g., ulcerative colitis, and normal donors. We detected G:C to A:T transitions in those nontumorous samples which were obtained from the donors where tumors also have G:C to A:T transitions. These transitions were observed with several-fold higher absolute mutation frequencies that the control samples from normal donors. Seven of ten ulcerative colitis samples showed several-fold higher absolute mutation frequency of G:C to A:T transition than in infants and normal adults. These initial results indicate that the nontumorous colon tissue in the cancer patients with p53 codon 248 mutations and the patient with ulcerative colitis carry a higher p53 mutation load at codon 248 that those from noncancer donors without known colon diseases.