Analysis of 4-ABP-DNA adducts and p53 alterations in urinary bladder carcinoma.
BACKGROUND
Activated intermediates of 4-aminobiphenyl (4-ABP) are able to covalently interact with DNA to form adducts. There is a large body of evidence indicating that carcinogen-DNA adduct formation can be one of the cancer initiating mechanisms.


METHODS
(4-ABP)-induced DNA damage in association with p53 overexpression and mutations were evaluated in specimens of urothelial bladder cancers from 106 patients.


RESULTS
4-ABP-DNA adduct levels resulted higher in smokers compared to non smokers, with a borderline statistical value. p53 nuclear overexpression was related to tumor grading, while no significant correlation with stage, 4-ABP-DNA adducts, smoking habit, and disease recurrence could be observed. Concerning molecular analysis, p53 point mutations were found in 17 of 106 cases (16%) and mutational pattern was significantly associated both with higher grade and stage, but no correlation was found with disease recurrence.


CONCLUSIONS
These results suggest that other sources, in addition to tobacco smoke, may contribute to 4-ABP-DNA adducts formation in bladder tissue and that p53 expression/mutation cannot be considered a prognostic factor in bladder cancer.
Romano
G
G
Giovanni XXIII Research Cancer Center, Institute of General Pathology, Catholic University School of Medicine, Rome, Italy. ibipg@rm.unicatt.it
Garagnani
L
L
Boninsegna
A
A
Ferrari
P
P
Flamini
G
G
De Gaetani
C
C
Sgambato
A
A
Giovanni
F
F
Curigliano
G
G
Ferretti
G
G
Cittadini
A
A
Trentini
G
G
D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D018736:DNA Adducts; D004273:DNA, Neoplasm / Q000378:metabolism*; D006801:Humans; D009367:Neoplasm Staging; D017354:Point Mutation; D012907:Smoking / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; C006757:4-biphenylamine