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p53 Mutations in Bladder Tumors from Arylamine-exposed Workers

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [J. A. T.]; University of North Carolina, Chapel Hill, North Carolina 27599 [Y. L., M. H., S. M., E. L.]; University of South Florida, Tampa, Florida 33612 [T. M.]; Roswell Park Memorial Institute, Buffalo, New York 14263 [C. M.]; and DuPont Specialty Chemicals, Deepwater, New Jersey 08023 [W. J. V.]

In this study we compared the frequency and pattern of p53 mutations in 34 bladder tumors from people with high-level occupational exposure to arylamines to those in 30 bladder tumors from people without such exposure. No differences were observed for p53 mutations between the two groups. The frequency of mutation was similar at 47% for arylamine-exposed individuals and 53% for unexposed individuals and showed a similar pattern of mutation, with GC to AT transitions accounting for the majority of the mutations in both groups. This finding suggest that arylamine exposure does not leave a mutational "footprint" in the p53 gene. However, compared to other tumors, bladder tumors from both exposed and unexposed individuals had a high frequency of multiple mutations and it is interesting that these mutations were highly concordant. We suggest that one explanation of this pattern of mutations could be from decreased DNA repair fidelity within tumor cells. The frequency of mutation in p53 is closely linked to tumor grade and stage and so may be a late event in the development of bladder tumers.

¹ To whom requests for reprints should be addressed, at National Institute of Environmental Health Sciences MD A3-05, P. O. Box 12233, Research Triangle Park, NC 27709.

Received 7/31/95. Accepted 11/ 8/95.

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