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Single Molecule Analysis of Laser Localized Psoralen Adducts
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[PAH-DNA adduct in human lung cancer explants. A preliminary study]
Objective:
To study the influences of external exposure on polycyclic aromatic hydrocarbons (PAH)-DNA adduct formation in lung cancer patients.
Methods:
On the basis of pilot experiments in mice, 32P post-labeling assay developed by Randerath was used to measure PAH-DNA adduct in human lung tissue explants. Relative adduct label(RAL) value was employed as a measure of adduct formation. A case-control study was designed using age-, sex-, and residence-matched patients with lung cancer and benign pulmonary diseases.
Results:
Although the mean RAL value in male lung cancer patients was not significantly different from that in patients with benign diseases, patients who smoked cigarettes had significantly higher RAL value than those who did not smoke(27.62 x 10(-9) versus 11.42 x 10(-9), P = 0.0015). In contrast, in female lung cancer patients, the RAL value was significantly higher in patients with lung cancer than in those with benign lung diseases (13.59 x 10(-9) versus 7.9 x 10(-9), P < 0.05). Moreover, significant difference in RAL values existed between female smokers and non-smokers. Cooking affected female patients only. Higher RAL values were seen in patients with squamous-cell carcinoma than with adenocarcinoma (P < 0.05). RAL values were significantly higher in poorly differentiated than in well-differentiated lung cancers (P < 0.05). A significant increase in RAL values was observed in patients with lymph node metastasis as compared with those without lymph node metastasis.
Conclusion:
PAH-DNA adduct level in lung tissue explants can be taken as a measure of environmental exposure and it correlates with the histological type, degree of differentiation and lymph node metastasis of lung cancer.
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