International Commission for Protection Against Environmental Mutagens and Carcinogens. Cyclosporine A: review of genotoxicity and potential for adverse human reproductive and developmental effects. Report of a Working Group on the genotoxicity of cyclosporine A, August 18, 1993.
Cyclosporine is an important therapeutic agent for transplant recipients and for a growing number of autoimmune diseases. Experimental animal and human data has indicated that cyclosporine is unlikely to be genotoxic. In contrast, azathioprine, an agent often given with cyclosporine, is considered to be genotoxic making the assessment of the independent effects of cyclosporine difficult. Cyclosporine does appear to be related to the development of tumors, primarily lymphomas, in animals and humans, but the basis of its potential carcinogenicity is not completely understood. In terms of reproductive and developmental toxicity, cyclosporine produces some adverse effects in both experimental animals and humans. In animals, the effects are seen at high doses sufficient to cause maternal toxicity. In humans, outcomes such as growth retardation have been noted, but the confounding effects of renal toxicity and resultant pregnancy complications cloud the interpretation. An increase in congenital anomalies and genetic disease have not been found reported in human studies that are limited in sample size. Given that the present data indicate the lack of genotoxicity, a mutation epidemiology study of cyclosporine is not recommended. As indicated above, such a study is probably impractical for many genetic endpoints of interest. However, well-conducted, large multicenter studies of transplant patients and their offspring would allow for routine monitoring of an increased risk for some reproductive and developmental (possibly non-genetic) endpoints that are of public health importance.
Olshan
A F
AF
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill 27599-7400.
Mattison
D R
DR
Zwanenburg
T S
TS
D000818:Animals; D001379:Azathioprine / Q000633:toxicity; D002869:Chromosome Aberrations; D016572:Cyclosporine / Q000009:adverse effects / Q000633:toxicity*; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced; D011241:Prednisone / Q000633:toxicity; D012098:Reproduction / Q000187:drug effects*
D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone