Assessment of toxicity, clastogenicity, mutagenicity and transforming activity of pentoxifylline in mammalian cells cultured in vitro.
We tested the possible cytotoxic, clastogenic and genotoxic effects of pentoxifylline on different lines of mammalian cells cultured in vitro. This study was part of the developmental research of agapurin, since pentoxifylline represents an effective compound of this drug. Cells treated for a short time manifested a relatively high resistance to the toxic effects of pentoxifylline. Generally, only cells treated for a long time (18 h) or a short time (2 h) with high concentrations of drug manifested sensitivity to the toxic effects of pentoxifylline. Although the tested drug induced DNA synthesis inhibition in V79 and EUE cells and clastogenic effects in V79 cells, it was not able to induce either 6-TGr mutations in the HGPRT locus of V79 cells or morphological transformation of Syrian hamster embryo cells. Adding of microsomal fraction S9 to the treated cells did not markedly change the effects of pentoxifylline on different studied endpoints. We suggest that pentoxifylline has no genotoxic effects, and that the cytotoxicity and induction of chromosomal aberrations were induced by inhibition of cellular DNA replication.
Slamenová
D
D
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
Dusinská
M
M
Gábelová
A
A
Horváthová
E
E
Oravec
C
C
Chalupa
I
I
Szabová
E
E
D000818:Animals; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D010431:Pentoxifylline / Q000633:toxicity*
D009153:Mutagens; D010431:Pentoxifylline