INDUCTION OF STABLE P53 ONCOPROTEIN AND OF C-MYC OVEREXPRESSION IN CULTURED NORMAL HUMAN UROEPITHELIUM BY RADIATION AND N-NITROSODIETHANOLAMINE

Uroepithelium cultured from normal patients without cancer (60 individ uals) was found to segregate into four subtypes based on the level of carcinogen treatment needed to induce abnormal p53 and c-myc. Twenty-t wo percent of patient cultures never showed abnormal p53 expression, e ven after chronic exposure to nitrosamines, in addition to irradiation . In these cultures, c-myc expression was confined to viable, normal-a ppearing cells at the growing edge of the culture and to apoptotic bod ies. Twenty-eight percent of cultures were negative for abnormal p53 u nless challenged with both radiation and chronic administration of nit rosamines, while a further 26% required only a single dose of radiatio n to induce the abnormal protein. The remaining patients had tissue wh ich, while initially negative for stable p53, became positive when put into culture and stimulated to grow. The c-myc protein was overexpres sed in all cultures with abnormal p53. It would appear that elevated e xpression of conformationally inactive p53 and of high levels of c-myc represents an early response of normal uroepithelial cells to carcino gen challenge. It also appears that a relatively high number of patien ts without cancer express these proteins when their cells are challeng ed to grow; a pre-exposure to environmental carcinogens such as nitros amines in cigarette smoke is likely to be involved.