Use of human-liver microsomes from kidney-transplant donors for the induction of chromatid aberrations and sister-chromatid exchanges by means of pre-carcinogens in Chinese hamster cells in vitro.
Samples of two human livers taken during operation of kidney donor patients were processed for microsome fractions and used for metabolization of cyclophosphamide (CP) and dimethylnitrosamine (DMN) in combination with the NADPH-generating system. Rat-liver microsomes were checked for comparison. Induction of chromatid aberrations and sister-chromatid exchanges in a newly isolated clone of Chinese hamster fibroblasts served as indicators of activity. Human S-9 fractions standardized on protein content showed strong variations of CP and DMN activation. Whereas liver microsomes of one patient (who also suffered from Gaucher's disease) were highly active for both pre-carcinogens and metabolized DMN at the same level as the uninduced rat-liver microsomes, the S-9 fraction from the second patient failed to activate CP, but was distinctly positive for DMN. It is suggested that samples of liver and other organs of renal transplant donors might be a practicable source of freshly prepared human microsome fractions usable in biochemical, genetic and carcinogenetic studies. Problems concerning the extrapolation of results are discussed.
D001711:Biotransformation; D002460:Cell Line; D002869:Chromosome Aberrations; D003434:Crossing Over, Genetic; D003520:Cyclophosphamide / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005821:Genetic Techniques; D006801:Humans; D016030:Kidney Transplantation; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*
D009153:Mutagens; D009602:Nitrosamines; D003520:Cyclophosphamide; D004128:Dimethylnitrosamine