C. Mothersill et al., INDUCTION OF STABLE P53 ONCOPROTEIN AND OF C-MYC OVEREXPRESSION IN CULTURED NORMAL HUMAN UROEPITHELIUM BY RADIATION AND N-NITROSODIETHANOLAMINE, Radiation research, 138(1), 1994, pp. 93-98
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.