Genetic characterization of adenovirus transformed cell revertants resistant to methylglyoxal bis(guanylhydrazone): Evidence for the involvement of three genetic loci
✍ Scribed by Nezha Alami; Arvind Chopra; Jean-Paul Thirion
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 784 KB
- Volume
- 147
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Five new independent rat somatic cell mutants resistant to the antileukemic drug methylglyoxal bis(guany1hydrazone) (MGBG) were isolated after mutagen treatmen[. The mutants were 7to 10-fold more resistant to MCBG than were the parental wild-type cells. When the MGBG-resistant (MGK) mutants were exposed to the drug in the presence of Tween-80, a nonionic detergent, they became as sensitive [MG') to MGBG as the wild-type cells, indicating that they were probably permeability mutants. Genetic analysis of hybrids between MGR mutants and wild-type cells showed the MGK and the nontransformed alleles to be recessive to the MG5 (wi Id-type) and transformed phenotype, respectively. Complementation analysis of the seven mutants revealed three functional genetic units or loci responsible not only for the M C R phenotype but also for tumorigenicity as determined in nude mice. Only the M C S hybrids produced tumors in the nude mice, whereas the MGR hybrids and mutants did not. Our results suggest the existence of cellular membrane components that are responsible both for cellular tumorigenicity and resistance to MGBG.