POLYCYCLIC AROMATIC-HYDROCARBONS ENHANCE TERMINAL CELL-DEATH OF HUMANECTOCERVICAL CELLS

Citation
Ea. Rorke et al., POLYCYCLIC AROMATIC-HYDROCARBONS ENHANCE TERMINAL CELL-DEATH OF HUMANECTOCERVICAL CELLS, International journal of oncology, 13(3), 1998, pp. 557-563
Citations number
60
Categorie Soggetti
Oncology
ISSN journal
10196439
Volume
13
Issue
3
Year of publication
1998
Pages
557 - 563
Database
ISI
SICI code
1019-6439(1998)13:3<557:PAETCO>2.0.ZU;2-T
Abstract
Polycyclic aromatic hydrocarbons (PAH) are a class of chemical carcino gens whose active metabolites form DNA adducts, resulting in specific mutational events. The tumor suppressor protein p53 is believed to pla y a pivotal role in the ability of cells to response to DNA damage, re sulting in either cell cycle arrest in G(1) or apoptosis under conditi ons Of excessive damage This growth inhibition it is associated with t he concomitant induction of p53 and enhanced terminal cell differentia tion. In this study we evaluated the effects of PAH on cell growth, ce ll differentiation, xenobiotic metabolism, and DNA adduct levels in no rmal ectocervical epithelial cells (ECE) and compared them to cervical cells whose p53 have been inactivated either by binding to viral HPV E6 oncogene (ECE16-1) or by mutation (C33A). The PAH 3-methylcholanthr ene (3MC) inhibited normal ECE and to a lesser extent ECE16-1 cell pro liferation. Not only did the growth inhibition occur at lower concentr ations in the normal cells but the extent of inhibition was also great er in normal as compared to immortalized cells. Benzanthracene (BA) ha d a minor effect on normal ECE cells with no effect on immortalized EC E16-1 cells. C33A cell growth was unaffected by 3MC and BA. Terminal c ell death was enhanced only in normal ECE cells as evidenced by increa sed envelope formation and was paralleled by an increase in the level of p53 following 3MC treatment. The differentiation status of the 3MC- treated cells was similar to untreated cells as indicated by three ind ependent markers of cell differentiation; transglutaminase, involucrin , keratin expression. There was no difference in the pattern or level of DNA adducts formed in normal and immortalized cells following 3MC t reatment. In addition the basal level of metabolism of C-14-BaP to phe nols, diols and quinnones was unaltered by pretreatment with either 3M C or BA. These results demonstrate that immortalized cervical cells ar e less sensitive to toxicant damage [i.e. cell proliferation and termi nal differentiation], and as a result, immortalized cells proliferate in the presence of genotoxic damage and are at increased risk for muta tions and cancer.