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6-methylmercaptopurine riboside resistance in human lymphocytes in the in vivo somatic cell mutation test

Journal Article · · Environ. Mutagen.; (United States)
Additional drug-resistance markers are being investigated to broaden the in vivo somatic cell mutation test in human lymphocytes (PBL). The adenosine kinase (AK) locus was chosen for study. The adenosine analog 6-methylmercaptopurine riboside (MeMPR) was used as the selective agent for obtaining AK-deficient mutants. Cultures of mitogen-stimulated PBL were set up in the presence (test) and absence (control) of the selective agent. Resistant cells capable of synthesizing DNA in the presence of MeMPR were labeled with tritiated thymidine and enumerated autoradiographically. Human PBL were found to be sensitive to MeMPR inhibition of DNA synthesis and exhibited a dose-dependent decrease in variant frequency (VF) with increasing concentrations of MeMPR. However, no leveling off of the dose-response curve was observed. It was concluded that, because of the autosomal recessive nature of the AK gene, the background Vf in human PBL is too low to allow a useful baseline to be established for the in vivo somatic mutation test.
Research Organization:
McMaster Univ., Hamilton, Ontario
OSTI ID:
5507366
Journal Information:
Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 8:3; ISSN ENMUD
Country of Publication:
United States
Language:
English