Lung cancer pathogenesis associated with wood smoke exposure.
BACKGROUND
Tobacco is considered the most important cause of lung cancer, but other factors could also be involved in its pathogenesis. The aim of the present work was to establish an association between wood smoke exposure and lung cancer pathogenesis, and to analyze the effects of wood smoke on p53 and murine double minute 2 (MDM2) protein expression.


METHODS
Blood samples were obtained from 62 lung cancer patients, 9 COPD patients, and 9 control subjects. Of the 62 lung cancer patients, 23 were tobacco smokers (lung cancer associated with tobacco [LCT] group), 24 were exposed to wood smoke (lung cancer associated with wood smoke [LCW] group), and 15 could not be included in these groups. Western blot assays were performed to identify the presence of p53, phospho-p53, and murine double minute 2 (MDM2) isoforms in plasma samples. Densitometric analysis was used to determine the intensity of p53, phospho-p53, and MDM2 bands.


RESULTS
Approximately 38.7% of the lung cancer patients examined had an association with wood smoke exposure, most of them women living in rural areas. Adenocarcinoma was present in 46.7% of these patients. The p53 and phospho-p53 proteins were significantly increased in LCW samples (56,536.8 +/- 4,629 densitometry units [DU] and 58,244.8 +/- 7,492 DU, respectively [+/- SD]), in comparison with the other groups. The 57-kD MDM2 isoform plasma concentration was very high in LCW and LCT samples (75,696.4 +/- 11,979 DU and 78,551.7 +/- 11,548 DU, respectively). MDM2-p53 complexes were present in a high concentration in control and COPD subjects. This allows p53 degradation and explains the low concentrations of p53 found in these groups. MDM2-phospho-p53 complexes were observed in COPD but not in the other samples. This correlates with the low concentration of p53 observed in the COPD group (13,657 +/- 2,012 DU), and could explain the different clinic evolution of this smoker population in comparison with the LCT subjects.


CONCLUSIONS
This study suggests that there is a possible association of lung cancer with wood smoke exposure. Likewise, our findings demonstrate that wood smoke could produce similar effects on p53, phospho-p53, and MDM2 protein expression as tobacco.
Laboratorio de Matriz Extracelular, Departamento de Enfermedades Crónico Degenerativas, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, CP 14080, Mexico, D.F., Mexico.
Javier
J
Delgado
Luis M
LM
Martinez
Therasa T
TT
Sánchez
Alejandra
A
Ramirez
Cecilia
C
Iturria
Georgina
G
González-Avila
D000230:Adenocarcinoma / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009687:Nuclear Proteins / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000097:blood; D051736:Proto-Oncogene Proteins c-mdm2; D012129:Respiratory Function Tests; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D014934:Wood
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012906:Smoke; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2