Analysis of p53, p16MTS, p21WAF1 and H-ras in archived bladder tumours from workers exposed to aromatic amines.
Exposure to aromatic amines is considered a major risk factor for the development of bladder cancer. In this study, we have analysed the pattern of point mutations in several tumour genes in 21 cases of bladder cancer arising among western European workers exposed to aromatic amines in an attempt to determine whether this exposure may be associated with a unique spectrum of mutations. Of the four genes analysed (p53, p16MTS1, p21WAF1 and H-ras), only p53 showed a high frequency of mutations (in 8 out of 21 cases, 38%). Two mutations were found in p16, one in H-ras and none in p21 exon 3. All mutations were at G:C base pairs, mostly at non-CpG residues. This spectrum of mutations, which is highly suggestive of an involvement of exogenous carcinogens, is however identical to the spectrum of p53 mutations detected in bladder cancers of the general population. In exposed workers, p53 mutations were associated with tumour grade and with high occupational and tobacco exposure. Taken together, our data suggest that the same carcinogens may be responsible for the development of bladder cancers in workers exposed to aromatic amines and in the general population.
Sørlie
T
T
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo.
Martel-Planche
G
G
Hainaut
P
P
Lewalter
J
J
Holm
R
R
Børresen-Dale
A L
AL
Montesano
R
R
D000293:Adolescent; D000328:Adult; D000588:Amines / Q000009:adverse effects*; D002273:Carcinogens; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced* / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000235:genetics*; D017354:Point Mutation; D012907:Smoking; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics*
D000588:Amines; C493956:CDKN1A protein, human; D002273:Carcinogens; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins