Pentoxifylline inhibits gene-specific repair of UV-induced DNA damage in hamster cells

✍ Scribed by Charles J. Link Jr.; David Orren; Rebecca Muldoon; John A. Cook; Vilhelm A. Bohr

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 613 KB
• Volume: 4
• Category: Article
• ISSN: 1065-7541
• DOI: 10.1002/(sici)1520-6823(1996)4:3<115::aid-roi3>3.0.co;2-0

✦ Synopsis

We have studied the effect of pentoxifyhe (PTX) on DNA repair after ultraviolet radiation 0 in Chinese hamster ovary cells (CHO). DNA repair of cyclobutane pyrimidine dimers (CPDs) was measured in the dihydrofolate reductase (DHFR) gene and in a downstream nontranscribed genomic region. Pentoxifylline (1 mM) inhibited the repair of CPDs in the hamster DHFR gene by 32% after 8 hr of repair incubation. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of W-induced cell killing by PTX. The W doses required for 37% survival after incubation with 0 and 1 mM PTX were 6.2 Jim' and 2.9 J/mz, respectively. This represents twofold more W-induced cytotoxicity in irradiated cells in the presence of PTX. We then evaluated the effect of PTX on RNA transcription and cell cycle kinetics. Incubation of W-irradiated CHO cells with PTX had no effect on the transcription of the DHFR gene. P T X did not produce a significant effect on cell cycle progression during 8 hr after UV-irradiation. However, by 24 hr afier irradiation, incubation with PTX induced a distinct block in early S-phase. We conclude that PTX sensitizes CHO cells to W-irradiation, perhaps because it inhibits DNA repair of active genes.