Abstract:
:The endogenous X-linked PIG-A gene is involved in the synthesis of glycosyl phosphatidyl inositol (GPI) anchors that tether specific protein markers to the exterior of mammalian cell cytoplasmic membranes. Earlier studies in rodent models indicate that Pig-a mutant red blood cells (RBCs) can be induced in animals treated with genotoxic agents, and that flow cytometry can be used to identify rare RBCs deficient in the GPI-anchored protein, CD59, as a marker of Pig-a gene mutation. We investigated if a similar approach could be used for detecting gene mutation in humans. We first determined the frequency of spontaneous CD59-deficient RBCs (presumed PIG-A mutants) in 97 self-identified healthy volunteers. For most subjects, the frequency of CD59-deficient RBCs was low (average of 5.1 ± 4.9 × 10(-6) ; median of 3.8 × 10(-6) and mutant frequency less than 8 × 10(-6) for 75% of subjects), with a statistically significant difference in median mutant frequencies between males and females. PIG-A RBC mutant frequency displayed poor correlation with the age and no correlation with the smoking status of the subjects. Also, two individuals had markedly increased CD59-deficient RBC frequencies of ∼300 × 10(-6) and ∼100 × 10(-6) . We then monitored PIG-A mutation in 10 newly diagnosed cancer patients undergoing chemotherapy with known genotoxic drugs. The frequency of CD59-deficient RBCs in the blood of the patients was measured before the start of chemotherapy and three times over a period of ∼6 months while on/after chemotherapy. Responses were generally weak, most observations being less than the median mutant frequency for both males and females; the greatest response was an approximate three-fold increase in the frequency of CD59-deficient RBCs in one patient treated with a combination of cisplatin and etoposide. These results suggest that the RBC PIG-A assay can be adopted to measuring somatic cell mutation in humans. Further research is necessary to determine the assay's sensitivity in detecting mutations induced by genotoxic agents acting via different mechanisms.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Dobrovolsky VN,Elespuru RK,Bigger CA,Robison TW,Heflich RHdoi
10.1002/em.20667subject
Has Abstractpub_date
2011-12-01 00:00:00pages
784-94issue
9eissn
0893-6692issn
1098-2280journal_volume
52pub_type
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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更新日期:2008-04-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
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doi:10.1002/1098-2280(2000)36:1<52::aid-em8>3.0.co;2-9
更新日期:2000-01-01 00:00:00
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更新日期:2008-07-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20166
更新日期:2006-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
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更新日期:2019-05-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22240
更新日期:2018-12-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850200103
更新日期:1992-01-01 00:00:00
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pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
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doi:10.1002/(sici)1098-2280(1997)29:1<73::aid-em10>3.0
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journal_title:Environmental and molecular mutagenesis
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doi:
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
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更新日期:2017-10-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
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更新日期:1991-01-01 00:00:00