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Reserch Of The Correlation Between Micronucleus And Tumor Formation

Posted on:2003-10-26Degree:MasterType:Thesis
Country:ChinaCandidate:E Z FengFull Text:PDF
GTID:2144360062490563Subject:Internal Medicine
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Lung cancer is the main disease threating human life, the mortality of which is gradully increasing. It is usually too late to diagnosis it with cytology and image method, when therapeutics opportunity will be lost. Therefore, it is urgent to find a new early diagnosis or predict method. Carcinogenesis is a complicated poly-stage procedure. It is generally accepted that oncogene activation and anti-oncogene inactivation are core of it, in which mutation of K-ras and p53 is a pair of most common event. It's a procedure of gene repairment against damage, immune surveillance against abnormal cell. When gene lesion that can not be repaired lead to endless proliferation of the involved cells, which can not be cleared, the tumor formation will be the result. Micronucleus is a reliable marker of chromosome damage and chromosomal instability. Investigations showed micronucleus frequency of target tissue cells, peripheral blood lymphocytes or exfoliat cells in patients with various tumor is high. Induced micronucleus frequency of them is also higher than health control. It is sugested that chromosomal instablity of patient with tumor contribute to the tumor susceptibility. To make clear the relation between micronucleus and tumor formation so as to investigate the micronucleus value in tumor diagnosis, we observed the changing of PBLMNF in rats when inducing lung tumor and the expression of K-ras, p53 and PCNA in lung tissue after the experiment. Moreover, we also observed PFLMNF, PBLMNF and induced-PBLMNF of some patients with benign or malignant pleural effusion. By comparing them, we try to discuss the significance of then in benign and malignant pleuraleffusion diagnosis.Results were as follows. Spontaneous PBLMNF and induced PBLMNFbetween treatment and control groups before the experiment had no statistics difference. Spontaneous PBLMNF and induced PBLMNF after treatment were significantly high than those before treatment, whereas it was not the case in control group in treatment group. At different time point after carcinogen administration, spontaneous or induced PBLMNF had no significant difference in treatment group. Spontaneous or induced PBLMNF in treatment group at varous stage after the treatment were notably higher than correspond records in control group. Correlation analysis showed that tumor number of per tumor-bearing rat was associated markedly with spontaneous PBLMNF at 6th or 10th week after the carcinogen administration. However, after adjustment for spontanous PBLMNF or body weight before treatment, there was no correlation between them. To predict tumor incidence in treatment group with spontaneous PBLMNF ^3 or induced PBLMNF 8 respectively showed high sensitivity and specificity at various stage after treatment in the tumor-induce group. Especially the criteria with induced PBLMNF exhibited better, the sensitivity and specificity are 88.89%~100%, 66.67%~100%, respectively. Expression rates of p53, K-ras and PCNA were 4/9> 3/9 and 9/9 respectively, which were all stained in tumor tissue cells. Normal tissue in treatment group and tissue in control group did not stained. Treatment group was divided into two subgroups according p53 and K-ras expressed or not. Comparision of various stage MNF between two subsections showed that MNF(include spontaneous and induced PBLMNF) in p53 positive subgroup was significantly higher than p53 negtive subgroup, whereas MNF in subgroups K-ras expressed or not showed no difference. Clinical study exhibited that spontaneous PBLMNF, induced PBLMNF and PFLMNF in patients with malignant pleural effusion were significantly higher than those with benign pleural effusion. PFLMNF was associated markedly with spontaneous and induced PBLMNF.These experiments indicated that micronuclei formation is a molecularbiology change in the early stage of tumor formation. It is associated with mutation of the anti-oncogen p53 and not related to oncogen K-ras' activation. Predetective diagnosis with spontaneous or induced PBLMNF in various stages exhibited high co...
Keywords/Search Tags:Micronuclei, Chromosomal stability, Lung neoplasm, Pleural effusion
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