[Roles of mutant p53 gene in malignant phenotypes and resistance to drugs in anti-7,8-dihydrodiol-9,10-epoxide benzo(a)pyrene-induced lung cancer cells].
OBJECTIVE
To study the role of mutant p53 gene induced by anti-7,8-dihydrodiol-9,10-epoxide benzo(a)pyrene (BPDE) in the development of lung cancer and the effects of wild-type p53 substitution on malignant phenotype and resistance to drugs.


METHODS
BPDE-induced human lung cancer cells (16HBE, a human bronchial epithelial cell line, treated by BPDE) with mutant p53 gene were transfected with pShuttle-cmv-wild p53, followed by soft-agar colony formation assay and cell growth assay. Genome DNAs were extracted from those cells after transfection for detection of apoptosis. Sensitivity of the cells to drugs was also detected simultaneously.


RESULTS
It was shown that exogenous wild-type p53 transfection inhibited colony formation of the lung cancer cells with mutant p53 gene and induced cell growth arrest and cell apoptosis. In addition, the lung cancer cells transfected with wild-type p53 gene showed enhanced sensitivity to adriamycin (ADM) to which the cells before transfection was resistant.


CONCLUSIONS
p53 mutation plays an important role in the development and progress of lung cancer, as well as in multi-drug resistance in the management of lung cancer chemotherapy. Wild-type p53 substitution therapy may enhance the sensitivity of lung cancer to chemical drugs.
Du
Chang-hu
CH
Guangzhou Respiratory Disease Institute, First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510120, China.
Xu
Jun
J
Zhong
Nan-shan
NS
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D017209:Apoptosis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D017354:Point Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide