Genotoxic effects linking cigarette smoking with lung cancer have not been consistently demonstrated, therefore claims for the cause-effect relationships are vigorously contested. Using matched populations of 22 lung cancer patients who have been cigarette smokers (LCP), 22 non-cancerous cigarette smokers (SC) and 13 non-smokers (NSC), we have applied the fluorescence in situ hybridization (FISH) tandem probe assay to elucidate the frequency of chromosome breakage among the participants. Two probes were used, a classical satellite probe which hybridizes to the large heterochromatin region of chromosome 1, and an α-satellite probe which targets a small region adjacent to the heterochromatin probe. The highest frequency of structural aberrations was observed in LCP (1.4 ± 0.1) followed by SC (1.25 ± 0.1) and NSC (0.4 ± 0.1). Aberration frequencies were not significantly different between LCP and SC (p > 0.05), however, a statistically significant difference was detected between the smoker populations combined (LCP and SC) and the NSC (p < 0.001). The breakage frequencies showed a positive correlation with duration of smoking for LCP (r = 0.5; p < 0.01), but not for SC (P > 0.05). In addition, the aberration frequencies were influenced by the inheritance of polymorphic glutathione S-transferase (GST) genes, LCPs missing one or the other GST (GSTM1 or GSTT1) genes were found to have significantly higher chromosome breaks compared to LCPs with both genes present (p < 0.05). Our data indicate that genetic predisposition and chromosome aberrations may be mechanistically related to the initiation of lung carcinogenesis; therefore, they may be useful biomarkers for lung cancer among cigarette smokers.
|Number of pages||7|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|State||Published - Sep 5 1997|
Bibliographical noteFunding Information:
This study was supported by a grant to W.W.A. from the U.S. Environmental Protection Agency (R821003010), the NIEHS Center (P30 ES 06676) from the US National Institute of Health and a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, to N.C.-F.
- Chromosome aberration
- Cigarette smoker
- Lung cancer
- Polymorphic GST gene
ASJC Scopus subject areas
- Molecular Biology
- Health, Toxicology and Mutagenesis