| First Author | Yadollahi-Farsani M | Year | 1997 |
| Journal | Br J Biomed Sci | Volume | 54 |
| Issue | 3 | Pages | 174-80 |
| PubMed ID | 9499594 | Mgi Jnum | J:43527 |
| Mgi Id | MGI:1098014 | Citation | Yadollahi-Farsani M, et al. (1997) Molecular mechanisms of mutagen hypersensitivity in adenine phosphoribosyl transferase-deficient Friend mouse erythroleukaemia cells. Br J Biomed Sci 54(3):174-80 |
| abstractText | Deficiency of the enzyme adenine phosphoribosyltransferase (APRT) has been associated with hypersensitivity to the mutagenic effects of ethyl methanesulphonate (EMS) and 254 nm ultraviolet (UV) radiation in clone 707 of Friend mouse erythroleukaemia (FEL) cells. The molecular nature of spontaneous EMS- and UV-induced mutations in the coding region of hypoxanthine-guanine phosphoribosyltransferase (HPRT) was determined for wild-type FEL cells and two APRT-deficient mutant sub-clones which have significantly reduced ATP pool levels, and are mutagen-hypersensitive. Mis-sense base substitutions were the predominant type of spontaneous mutation. However, exon deletions, possibly involving aberrant splicing of HPRT mRNA, and a non-sense mutation were also observed. EMS-induced mutations in wild-type and APRT-deficient mutant sub-clones were GC-->AT transitions, which is consistent with O6-ethylguanine being the primary pre-mutagenic lesion. All UV-induced mutations in both cell types were targeted to dipyrimidine sites where the two most common classes of photoproducts (cyclobutane pyrimidine dimers and [6-4] photoproducts) are formed. The similarity in the mutations observed in both cell types indicates that the mutagen hypersensitivity of APRT-deficient cells may be the result of decreased efficiency in the excision repair processes due to reduced levels of ATP. |
