Codominant and recessive 9-beta-D-arabinofuranosyladenine-resistant mutations of baby hamster cells.
9-beta-D-Arabinosyladenine (araA)-resistant mutants of baby hamster kidney (BHK) cells can be classified into 3 classes. In order to gain a better understanding of the mechanism(s) of resistance and the biochemical basis of cytotoxicity of various purine nucleosides, cell hybrids of the mutant and wild-type cells were made and analyzed. The class I araA-resistant, adenosine-kinase-deficient (AK-) allele was shown to be recessive to the wild-type araA-sensitive (AK+) gene. The class II mutant allele, which encodes an altered ribonucleoside diphosphate reductase, was shown to be codominant. The class III mutants show multiple phenotypes, araAr/dAdor/adenosine sensitive (Ados) and alteration in AK activity. The araA- and dAdo-resistant alleles of araS10d, ara-16c, and ara-19a in class III mutant/wild-type hybrid cells are all recessive to the wild-type allele, consistent with a common mechanism of resistance. In contrast the Ados allele of ara-S10d is dominant while those of ara-16c and ara-19a are recessive. The difference may be a reflection of two distinct mechanisms of enhanced Ado sensitivity or, alternatively, it suggests that the sensitivity of the hybrids to Ado is highly dependent on the level of AK activity.
D000248:Adenosine Kinase / Q000235:genetics; D000483:Alleles; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004351:Drug Resistance; D005799:Genes, Dominant; D005808:Genes, Recessive; D006822:Hybrid Cells / Q000187:drug effects; D007668:Kidney; D009154:Mutation; D014740:Vidarabine / Q000494:pharmacology*
D000248:Adenosine Kinase; D014740:Vidarabine