ATLA::Alternatives to Laboratory Animals

Volume 23, Number 4

Toxicity, clastogenicity and genotoxicity of theophylline and pentoxifylline in mammalian cells cultured in vitro.

ATLA 23, 504-512, July/August 1995

Darina Slamenová, Ivan Chalupa, Alena Gábelová, Eva Bozsakyová, Eva Horváthová and Milan Blasko

Cancer Research Institute, Slovak Academy of Sciences, Spitalska 21, 812 32 Bratislava, Slovakia

SUMMARY

As part of a developmental study on theophylline and pentoxifylline, these drugs were tested for possible cytotoxic, mutagenic and clastogenic effects on V79 hamster cells and human Iymphocytes cultured in vitro. After the short-term treatment of V79 cells with theophylline and pentoxifylline the cells were relatively resistant to the toxic effects of these methylxanthines. Generally, only high concentrations of theophylline or pentoxifylline had toxic effects on exposed V79 cells. Short-term treatment of V79 cells with theophylline or pentoxifylline did not induce 6-thioguanine resistant mutations in either the presence or absence of SO fractions. However, in the absence of an S9 fraction, elevated levels of single-strand breaks in DNA were induced. Both methylxanthines caused clastogenic effects in human Iymphocytes and hamster V79 cells after long-term exposure. We suggest that theophylline and pentoxifylline are clastogenic but not genotoxic, and that the molecular mechanism for the induction of single-strand breaks in DNA and the induction of chromosomal aberrations in cells treated with theophylline and pentoxifylline is not the induction of lesions in the DNA but the inhibition of DNA chain elongation.

Keywords: methylxanthines, theophylline, pentoxifylline, human Iymphocytes, Chinese hamster V79 cells, gene mutations, single-strand DNA breaks, clastogenicity