Genetic risks of antiviral nucleoside analogues--a survey.
The available informations on the genotoxic effects in experimental systems of the antiherpesvirus nucleosides aciclovir, penciclovir, ganciclovir, brivudine and cidofovir as well as of the antiretrovirals zidovudine (AZT), lamivudine, zalcitabine (ddC), didanosine and stavudine are reviewed. Furthermore, data on carcinogenic activity of these drugs in laboratory rodents are compiled. Most nucleoside analogue antivirals induce chromosomal aberrations but are inactive in gene mutation assays. Carcinogenicity findings in mice and rats are variable but clearly positive for AZT and ddC. The possible mechanisms by which these agents may cause damage in the genetic information are still largely hypothetical, and experimental findings do not permit relevant extrapolations to the situation in man. There is no conclusive evidence that any of the drugs caused tumours in humans. The use of nucleoside analogues in antiviral therapy remains a pragmatic option that seems justified by risk/benefit assessment.
Wutzler
P
P
Institute for Antiviral Chemotherapy, Friedrich Schiller University of Jena, Winzerlaer Str. 10, 07745, Jena, Germany.
Thust
R
R
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects* / Q000737:chemistry / Q000633:toxicity; D015197:Carcinogenicity Tests; D002273:Carcinogens; D002869:Chromosome Aberrations; D006801:Humans; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009705:Nucleosides / Q000009:adverse effects* / Q000737:chemistry / Q000633:toxicity
D000998:Antiviral Agents; D002273:Carcinogens; D009153:Mutagens; D009705:Nucleosides