Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers.
Ionizing radiation is a potent lung carcinogen, but the precise molecular damage associated with it is still unknown. In this study we investigated cancer-related molecular abnormalities including K-ras (codon 12) mutation, p16(INK4A) promoter hypermethylation and microsatellite alterations at seven chromosomal regions in successive biopsies obtained from former Chernobyl cleanup workers in comparison with smokers and nonsmokers who have never had radiation exposure. Our results indicate that prolonged persistence of inhaled radioactive particles is associated with appearance of allelic loss at 3p12, 3p14.2 (FHIT), 3p21, 3p22-24 (hMLH1) and 9p21 (p16INK4A) in bronchial epithelium of former Chernobyl clean-up workers. The prevalence of 3p14.2 allelic loss was associated with decreased expression of the FHIT mRNA in their bronchial epithelium in comparison with control group of smokers. During several years of our monitoring samples of epithelium were collected from the same area of bronchial tree. In epithelium exposed to carcinogens (tobacco smoke and/or radioactivity) the total number of molecular abnormalities was significantly higher in dysplasia and in morphologically normal foci progressed later to dysplasia than in these samples which never showed evidence of such progression. Our findings indicate that extensive cancer-related molecular abnormalities sequentially occur in radiation damaged bronchial epithelium of former Chernobyl clean-up workers.
Chizhikov
Victor
V
Cancer Research Center, Moscow, Russia.
Chikina
Svetlana
S
Gasparian
Alexander
A
Zborovskaya
Irina
I
Steshina
Ekaterina
E
Ungiadze
Guram
G
Samsonova
Maria
M
Chernyaev
Andrei
A
Chuchalin
Alexander
A
Tatosyan
Alexander
A
D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D001982:Bronchial Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005500:Follow-Up Studies; D011905:Genes, ras / Q000528:radiation effects; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009784:Occupational Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016273:Occupational Exposure; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011832:Radiation Injuries / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011839:Radiation, Ionizing; D018788:Radioactive Hazard Release; D020545:Respiratory Mucosa / Q000473:pathology / Q000528:radiation effects; D012907:Smoking; D014455:Ukraine; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase