Role of DNA repair in carcinogen-induced ras mutation

Engelbergs, Jörg; Thomale, Jürgen; Rajewsky, Manfred F.

doi:10.1016/s0027-5107(00)00021-x

Cited by 30 publications

(19 citation statements)

References 93 publications

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“…The rice gene encoding Pho1 spans 6768 bp and consists of 15 exons and 14 introns ( Figure 5A). MNU almost exclusively induces G:C to A:T transitions in mammalian genes (Engelbergs et al, 2000;Cooks et al, 2003). A similar tendency of mutagenesis by MNU was found in the treatment of the fertilized egg cell in rice, in which most of the mutations were observed to be nucleotide transitions of G:C to A:T by TILLING analysis (Suzuki et al, 2008).…”

Section: Analysis Of Nucleotide Sequences Of the Pho1 Gene From The Psupporting

confidence: 63%

Mutation of the Plastidial α-Glucan Phosphorylase Gene in Rice Affects the Synthesis and Structure of Starch in the Endosperm

et al. 2008

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Plastidial phosphorylase (Pho1) accounts for ;96% of the total phosphorylase activity in developing rice (Oryza sativa) seeds.From mutant stocks induced by N-methyl-N-nitrosourea treatment, we identified plants with mutations in the Pho1 gene that are deficient in Pho1. Strikingly, the size of mature seeds and the starch content in these mutants showed considerable variation, ranging from shrunken to pseudonormal. The loss of Pho1 caused smaller starch granules to accumulate and modified the amylopectin structure. Variation in the morphological and biochemical phenotype of individual seeds was common to all 15 pho1-independent homozygous mutant lines studied, indicating that this phenotype was caused solely by the genetic defect. The phenotype of the pho1 mutation was temperature dependent. While the mutant plants grown at 308C produced mainly plump seeds at maturity, most of the seeds from plants grown at 208C were shrunken, with a significant proportion showing severe reduction in starch accumulation. These results strongly suggest that Pho1 plays a crucial role in starch biosynthesis in rice endosperm at low temperatures and that one or more other factors can complement the function of Pho1 at high temperatures.

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Section: Analysis Of Nucleotide Sequences Of the Pho1 Gene From The Psupporting

confidence: 63%

Mutation of the Plastidial α-Glucan Phosphorylase Gene in Rice Affects the Synthesis and Structure of Starch in the Endosperm

et al. 2008

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“…Substitutions from G to A and C to T were 50% and 42%, respectively, as expected from alkylation of the guanine residue by MNU (Engelbergs et al 2000, Jansen et al 1994 and the remaining two were transversions from AT to TA. Similar results were obtained for mutagenesis of other genes , She et al 2010, providing further evidence that MNU induces predominantly GC to AT transitions in plants, as well as in microbes and vertebrates.…”

Section: Type Of Mutations Derived From Mnu Treatment Of Fertilized Ementioning

confidence: 77%

“…The mutagenesis of DNA by nitrosamides starts with the methylation of bases, especially guanine and cytosine. O 6 -methylguanine, induced in DNA by MNU treatment, gave rise to GC to AT transition mutations via mispairing with thymine during DNA replication (Cooke et al 2003, Engelbergs et al 2000. A number of studies on alkyl nitrosourea induced rodent tumors have shown that methylating N-nitroso carcinogens almost exclusively induced GC to AT transitions in the genes analyzed (Calvert et al 1996, Guzman et al 1992, Newcomb et al 1995, Ohgaki et al 1992, Sukumar et al 1983, Sukumar and Barbacid 1990, You et al 1989, Zaidi et al 1995, Zarbl et al 1985.…”

Section: Chemical Properties Of Nitroso Compoundsmentioning

confidence: 99%

Use of N-methyl-N-nitrosourea treatment of fertilized egg cells for saturation mutagenesis of rice

2010

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The efficiency of N-methyl-N-nitrosourea (MNU) treatment of fertilized egg cells at the single-cell stage in rice (Oryza sativa L.) was about twice that of dry seeds. The proportion of recessive iso-chlorophyll mutants in the segregating progeny of M 1 plants decreased remarkably with treatment at later stages of embryonic development, perhaps because of the presence of diplontic selection and chimera formation when older, multicellular embryos were mutagenized. Panicle sterility of the M 1 plants showed a linear relationship with the frequency of chlorophyll mutations in the progeny. The mutagenicity of N-ethyl-N-nitrosourea was similar to that of MNU, but N-methyl-N′-nitro-N-nitrosoguanidine and N-ethyl-N′-nitro-N-nitrosoguanidine were less effective. Several thousand rice mutants affecting endosperm, culm length, heading date, and chlorophyll were obtained by MNU mutagenesis. The frequency of certain types of endosperm mutants seemed to differ according to the precise timing of treatment. The mutation rate was calculated as 7.4 × 10 −6 per nucleotide, and the mutations were evenly distributed over the gene regions examined. These results indicate that our rice mutant library, generated by MNU mutagenesis, is a promising resource for identifying mutations in any rice gene.

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“…Previous studies have reported that ENU affected the expression of genes such as p21-Ras (Engelbergs et al 2000) and p53 (Katayama et al 2005a;Mukherjee et al 2006), closely related to the modulation of morphogenic and The graph shows concentrations of VEGF 165 obtained by ELISA assay for samples with normal blood content (blue box) and for samples of exsanguinated animals after perfusion with saline (green box). The differences between conditions was of p<0.05 and among groups (control, CO classic oligodendroglioma and AO anaplastic oligodendroglioma) of p<0.001.…”

Section: Vegf Expressionmentioning

confidence: 99%

VEGF Immunopositivity Related to Malignancy Degree, Proliferative Activity and Angiogenesis in ENU-Induced Gliomas

Bulnes

Lafuente

2007

J Mol Neurosci

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Growth of solid tumors is highly dependent on angiogenesis. During tumor development, neoplastic cells switch to an angiogenic phenotype, playing a significant role in the expression of the vascular endothelial growth factor (VEGF). Seventy-two brain gliomas were induced in Sprague Dawley rats by prenatal exposure to ethylnitrosourea (ENU). Screening and location of tumors was carried out using magnetic resonance imaging (MRI). Conventional histology and immunocytochemistry for antibodies against glial fibrillary acidic protein (GFAP), S-100, NF, oligodendrocyte Ab-2, Ki-67, and VEGF165 were performed. The proliferation index (PI) was calculated from the Ki-67 labeling index, and the concentration of VEGF165 was quantified by enzyme-linked immunosorbent assay (ELISA). In vivo identification of macro- and microtumor appears to be useful to lead morphological and biochemical studies. Histopathology allows us to identify microtumors as classic oligodendrogliomas (CO; mean PI of 6.01 +/- 2.8%) and macrotumors as anaplastic oligodendrogliomas (AO; mean PI of 14.06 +/- 5%). Classic oligodendrogliomas show scarce VEGF165 expression whereas anaplastic ones display VEGF165 protein level 100-fold increased respect to CO. Astrocytes, neoplastic, and endothelial cells show differential immunostaining patterns from the border to the core of neoplasm. Positive structures for VEGF and their distribution vary according to PI increase. Anaplastic gliomas displaying VEGF-positive intratumor capillaries correspond to the highest PI values. To identify the "angiogenic switch," we propose the glioma stage characterized by VEGF immunopositive neoplastic cells inside the tumor and positive endothelial cells surrounding it.

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Role of DNA repair in carcinogen-induced ras mutation

Cited by 30 publications

References 93 publications

Mutation of the Plastidial α-Glucan Phosphorylase Gene in Rice Affects the Synthesis and Structure of Starch in the Endosperm

Mutation of the Plastidial α-Glucan Phosphorylase Gene in Rice Affects the Synthesis and Structure of Starch in the Endosperm

Use of N-methyl-N-nitrosourea treatment of fertilized egg cells for saturation mutagenesis of rice

VEGF Immunopositivity Related to Malignancy Degree, Proliferative Activity and Angiogenesis in ENU-Induced Gliomas

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