Malignant transformation of human prostate epithelial cells by N-nitroso-N-methylurea.
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.
Rhim
J S
JS
Laboratory of Biochemical Physiology, National Cancer Institute, Frederick, Maryland 21702, USA.
Jin
S
S
Jung
M
M
Thraves
P J
PJ
Kuettel
M R
MR
Webber
M M
MM
Hukku
B
B
D000328:Adult; D000818:Animals; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations / Q000139:chemically induced*; D025063:Chromosome Disorders; D006801:Humans; D007621:Karyotyping; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D018631:ras Proteins / Q000032:analysis
D002273:Carcinogens; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D008770:Methylnitrosourea; D018631:ras Proteins