DNA damage and activation of c-ras in human embryo lung cells exposed to chrysotile and cigarette smoking solution.
Epidemiological studies and animal experiments showed that asbestos and cigarette smoking can act synergistically in the development of lung cancer. The mechanism of this synergism is largely unknown. It is well documented that DNA damage and activation of oncogenes play important roles in the development of cancer. The aim of our study was to find out if DNA damage could be increased and c-ras oncogene could be activated when human embryo lung cells were treated with chrysotile (CH) and cigarette smoking solution (CSS) separately or simultaneously. Human embryo lung (HEL) cells were treated with different doses of CH and CSS separately or simultaneously, then DNA strand breaks were detected with single-cell gel electrophoresis assay and the expression of p21 was detected by flow cytometry. Factorial analysis was used to evaluate the combined effect of chrysotile and cigarette smoking solution. The results showed that DNA strand breaks could be increased significantly when HEL cells were exposed to CH and CSS separately for 1 hour and increased in a dose-dependent relationship when cells were exposed to CH and CSS simultaneously for 1 hour. The expression of p21 increased significantly when cells were exposed to CH for 24 hours, but there was no significant increase when cells were exposed to CSS for 24 hours. However, there was an additive effect on the expression of p21 when cells were exposed to CH and CSS simultaneously for 24 hours. When cells were exposed to CH and CSS simultaneously three times (24 hours each time), then passaged for 1 month, the expression of p21 increased synergistically. In conclusion, DNA damage and activation of c-ras may be involved in the process of combined carcinogenesis of CH and CSS.
Wang
Q
Q
Department of Occupational Health, Beijing Medical University, China.
Fan
J
J
Wang
H
H
Liu
S
S
D017632:Asbestos, Serpentine / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012907:Smoking; D013638:Tars / Q000494:pharmacology*
D017632:Asbestos, Serpentine; D013638:Tars; C024746:tobacco tar; D004247:DNA; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)