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Laboratory of Biochemical Physiology, National Cancer Institute, Building 567, Frederick, Maryland 21702 [J. S. R., S. J.]; Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University School of Medicine, Washington, D.C. [M. J., P. J. T., M. R. K.]; Departments of Medicine and Zoology, Michigan State University, East Lansing, Michigan 48824 [M. M. W.]; and Cell Culture Laboratory, Children's Hospital of Michigan, Detroit, Michigan 48201 [B. H.]
We report the malignant transformation of adult human prostate epithelial cells after multiple exposures to the chemical carcinogen N-nitroso-N-methylurea. Such transformants showed morphological alterations and anchorage-independent growth in soft agar and induced carcinomas when transplanted into nude mice. No p53 or ras mutations were observed. Stepwise chromosomal changes in the progression to tumorigenicity were observed. Loss of the p arms of chromosome 8 (p10>pter) and chromosome 10 (p10>pter) and gain of the q arm of chromosome 8 (q10>qter) were only observed in the tumor outgrows. These findings provide the first evidence of malignant transformation of human prostate epithelial cells exposed to a chemical carcinogen.
1 To whom requests for reprints should be addressed. Phone: (301) 846-1592; Fax: (301) 846-6863.
Received 11/ 1/96. Accepted 1/ 4/97.
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