Molecular Biological Responses of TCDD Transformed Human Keratinocytes Induced by UVB Irradiation

Ham, Hee Jung; Kim, Dae Kwang; Han, Ki Hwan

Abstract

The expression of nm23-H1, nm23-H2, p53, c-myc, cyclin D1, and k-ras genes were investigated in TCDD transformed human keratinocyte RHEK1 cells by exposure to UVB 200 J/m2. For 3 days after irradiation the transcriptional kinetics of these genes were evaluated. The expression of nm23-H1 and H2 were highly increased at 6 hours post-irradiation and recovered in about 3 days to level of pre-irradiation. In cyclin D1 there was a temporary increased expression at 3 hours post-irradiation, but after that time its expression increased minimally. The kinetic of p53 expression was not constant, but showed a decreased tendency. K-ras expression level was decreased by degrees. The decrease in c-myc expression might be related to wavelength-specific induction. In this experiment, S-phase prolongation was a typical alternation in early phase after UVB irradiation. The decreased p53 and k-ras expression and the increased expression of cyclin D1 pushed G1-epsilonS phase transition, and during prolonged S-phase the increased expression of nm23-H1 and H2 might be involved in cell cycle progression, suggesting a function concomitant with prolongation of S-phase after UVB irradiation. TCDD transformed human keratinocyte RHEK1 cell line had 2 heterogeneous cell clones, near diploid and hypotetraploid, and were more resistant against UVB irradiation than RHEK1 cell line. And it had S-phase prolongation instead of G1 arrest in response to UVB irradiation, which may have negative effect to be accumulated DNA mutation without DNA repair.