Ionizing radiation-induced mutagenesis

Breimer, LH

doi:10.1038/bjc.1988.2

Cited by 150 publications

(53 citation statements)

References 194 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The dose response was curvilinear on an arithmetic plot (of clonogenic mutant axis) but approximately linear when a log scale was used as shown. This pattern of dose response is similar to that reported before for hprt mutations induced by high dose rate of g or X-irradiation in mouse and human cells (Furono-Fukushi et al, 1993;Vijayalaxmi and Evans, 1984) and is attributed to hprt mutations arising by chromsome aberrations (Vijayalaxmi and Evans, 1984) b Radiation-induced mutation in p53 null cells SD Griffiths et al rodent cells which indicated that a large fraction of radiation-induced hprt gene mutants had lost all coding sequences (Breimer, 1988). The frequency of hprt mutants following radiation might be an overestimate due to the overgrowth of dominant clones in the culture system.…”

Section: P53 Expression and Clonogenic Survival After Irradiationsupporting

confidence: 87%

Absence of p53 permits propagation of mutant cells following genotoxic damage

et al. 1997

View full text Add to dashboard Cite

Much evidence has been gathered in support of a critical role for p53 in the cellular response to DNA damage. p53 dysfunction is associated with progression and poor prognosis of many human cancers and with a high incidence of tumours in p53 knockout mice. The absence of a p53-dependent G 1 arrest that facilitates DNA repair or apoptosis might impact critically on clinical cancer in two ways. First, by abrogating the impact on therapy that operates via genotoxic damage and apoptosis; and second, by encouraging progression either by inducing genomic instability and DNA mis-repair or by permitting survival of mutants. However, experiments examining the relationship between p53 de®ciency and mutation frequency have so far failed to con®rm these predictions. The precise role played by p53 is therefore unclear. We now report use of a short term in vitro approach to assess the in¯uence of p53 on radiation-induced mutations at the hprt locus in murine B cell precursors that are normally radiation ultrasensitive. We ®nd a high number of hprt mutants among X-irradiated p53 null cells, which results from preferential survival as clonogenic mutants rather than from a p53-dependent increase in mutation rate. This result has important implications for genotoxic cancer therapy.

show abstract

Section: P53 Expression and Clonogenic Survival After Irradiationsupporting

confidence: 87%

Absence of p53 permits propagation of mutant cells following genotoxic damage

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Mammalian cells exposed to ionizing radiation also frequently display increased mutations (35,36). Precisely which genome lesion(s) lead to mutations has not been firmly established (31).…”

Section: Resultsmentioning

confidence: 99%

Mouse embryonic stem cells carrying one or two defective Msh2 alleles respond abnormally to oxidative stress inflicted by low-level radiation

DeWeese

Shipman

Larrier

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

173

108

View full text Add to dashboard Cite

Chronic oxidative stress may play a critical role in the pathogenesis of many human cancers. Here, we report that mouse embryonic stem (ES) cells deficient in DNA mismatch repair responded abnormally when exposed to low levels of ionizing radiation, a stress known to generate oxidative DNA damage. ES cells derived from mice carrying either one or two disrupted Msh2 alleles displayed an increased survival following protracted exposures to low-level ionizing radiation as compared with wild-type ES cells. The increases in survival exhibited by ES cells deficient in DNA mismatch repair appeared to have resulted from a failure to efficiently execute cell death (apoptosis) in response to radiation exposure. For each of the ES cell types, prolonged low-level radiation treatment generated oxidative genome damage that manifested as an accumulation of oxidized bases in genomic DNA. However, ES cells from Msh2 ؉͞؊ and Msh2 ؊͞؊ mice accumulated more oxidized bases as a consequence of low-level radiation exposure than ES cells from Msh2 ؉͞؉ mice. The propensity for normal cells with mismatch repair enzyme deficiencies, including cells heterozygous for inactivating mismatch repair enzyme gene mutations, to survive promutagenic genome insults accompanying oxidative stresses may contribute to the increased cancer risk characteristic of the hereditary nonpolyposis colorectal cancer syndrome.

show abstract

“…While it is known that the effective- ness of the UvrABC excision repair system of Escherichia coli is affected by the nucleotides near a damaged base (25) and that DNA damage produced by gamma radiation is often repaired in mammalian cells (23), it is unknown whether mammalian repair enzymes are affected by the DNA sequence near a damaged base. Neutron-induced damage may be more difficult to repair because neutrons are thought to produce dense clusters of lesions in DNA molecules (26).…”

Section: Comparison Between Neutron and Gamma Radiation In Ras Mutatimentioning

confidence: 99%

“…Gamma radiation damages DNA indirectly through the production of free radicals (23), and the conformation of DNA and DNA-protein interactions could affect the damage created by free radicals (24).…”

Section: Comparison Between Neutron and Gamma Radiation In Ras Mutatimentioning

confidence: 99%

ras activation in human tumors and in animal model systems.

Corominas

Sloan

León

et al. 1991

Environ Health Perspect

View full text Add to dashboard Cite

Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. We have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbezanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. We found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel Kras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation.

show abstract

Ionizing radiation-induced mutagenesis

Cited by 150 publications

References 194 publications

Absence of p53 permits propagation of mutant cells following genotoxic damage

Absence of p53 permits propagation of mutant cells following genotoxic damage

Mouse embryonic stem cells carrying one or two defective Msh2 alleles respond abnormally to oxidative stress inflicted by low-level radiation

ras activation in human tumors and in animal model systems.

Contact Info

Product

Resources

About