Effect of pentoxifylline on radiation damage and tumor growth.
OBJECTIVE
Inactivation of tumor cells by photon irradiation can be markedly improved by tumor oxygenation. We have investigated the effect of the vasoactive drug pentoxifylline with respect to cell toxicity, radiation sensitivity, repair and tumor growth.


METHODS
V79 and Hela cell survival curves and determination of the tumor volume using rhabdomyosarcoma growth in BALB/c mice.


RESULTS
In the presence of 1 mM pentoxifylline, survival of V79 Chinese hamster lung fibroblasts and human Hela cells at a dose level of 2 Gy is reduced by factors of 1.12 +/- 0.09 and 1.62 +/- 0.10 S.E. respectively. A radiosensitizing effect of pentoxifylline is also evident from the change of the alpha-coefficient which increases from 0.140 to 0.19 and from 0.39 to 0.65 in V79 and Hela cells respectively. In 3 h split dose experiments Hela cells but not V79 cells showed a change in the recovery ratio from 3.0 in control cells to 1.0 in drug exposed cells. In vivo experiments on BALB/c mice receiving 50 mg/kg pentoxifylline alone by subcutaneous injection showed a marked stimulation of tumor growth. When combined with irradiation we observed a 1.3 to 1.7 fold gain in tumor growth delay depending upon tumor size or day of measurement.


CONCLUSIONS
The results suggest that pentoxifylline has an intrinsic effect on cell recovery and in tumors also improves blood supply and oxygenation.
Vernimmen
F
F
Department of Radiotherapy, Tygerberg Hospital, Republic of South Africa.
Verheye-Dua
F
F
du Toit
H
H
Böhm
L
L
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D006224:Cricetinae; D003412:Cricetulus; D004354:Drug Screening Assays, Antitumor; D005720:Gamma Rays / Q000009:adverse effects; D006367:HeLa Cells; D006801:Humans; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D010431:Pentoxifylline / Q000627:therapeutic use* / Q000633:toxicity; D011836:Radiation Tolerance / Q000187:drug effects*; D012208:Rhabdomyosarcoma / Q000139:chemically induced / Q000188:drug therapy* / Q000532:radiotherapy*
D008748:Methylcholanthrene; D010431:Pentoxifylline