Studies of mutagenicity and clastogenicity of 5-azacytidine in human lymphoblasts and Salmonella typhimurium.
5-Azacytidine (5-AzaC) induced mutation in the TK+/- human lymphoblastoid line, TK6, at both the thymidine kinase (tk) locus as measured by resistance to trifluorothymidine (F3TdR), and the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus, as measured by resistance to 6-thioguanine (6TG). F3TdRR and 6TGR mutant fractions induced by 5-AzaC were observed after a normal phenotypic expression time and remained stable. Interestingly, 5-AzaC was 5-10 times more mutagenic at the tk locus than the hgprt locus. However, F3TdRR colonies from 5-AzaC-treated cultures behaved like TK-deficient mutants induced by other chemical mutagens. The TK or HGPRT phenotype had no effect on the toxicity of 5-AzaC, thus eliminating differential toxicity as a potential cause for the observed higher mutability at the tk locus. 5-AzaC did not induce F3TdRR cells in the parental TK+/+ lymphoblastoid line, indicating that 5-AzaC-induced F3TdRR variants were not due to a dominant alteration in gene expression. 5-AzaC did not induce chromosomal aberrations in TK6 cells, eliminating clastogenic events as a potential cause for the higher mutability at the tk locus. 5-AzaC was also found to be mutagenic in a forward mutation assay to 8-azaguanine resistance in Salmonella typhimurium.
K M
KM
Call
J C
JC
Jensen
H L
HL
Liber
W G
WG
Thilly
D001374:Azacitidine / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects*; D013937:Thymidine Kinase / Q000235:genetics
D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; D001374:Azacitidine