Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats

Zarbl, Helmut; Sukumar, Saraswati; Arthur, Anne V.; Martı́n-Zanca, Dionisio; Barbacid, Mariano

doi:10.1038/315382a0

Cited by 786 publications

(385 citation statements)

References 21 publications

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“…In contrast, subgroup analysis of specific point mutations in the K-ras gene showed that high consumption of meat products is positively associated with rectal tumours harbouring a G4A transition. Although the association was not statistically significant, this observation is in line with the biological evidence (Zarbl et al, 1985;Topal, 1988;Jacoby et al, 1992;Hughes et al, 2001;Bingham et al, 2002). Why the association in our study is confined to the rectum and not to the colon remains unclear.…”

Section: Discussionsupporting

confidence: 87%

“…Alkylating DNA agents like nitrosamines could generate O 6 -methylguanines and these have been detected in human colonic tissue (Hall et al, 1991). N-nitroso compounds could also induce G4A transitions in codons 12 or 13 of the K-ras gene of rat colon carcinomas (Zarbl et al, 1985;Topal, 1988;Jacoby et al, 1992) or in human colonic tissue (Hughes et al, 2001;Bingham et al, 2002). In the current study, no clear association was observed for daily consumption of meat products and overall colon and rectal cancer risk.…”

Section: Discussionmentioning

confidence: 99%

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Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

et al. 2005

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Case -cohort analyses were performed on meat and fish consumption in relation to K-ras mutations in 448 colon and 160 rectal cancers that occurred during 7.3 years of follow-up, excluding the first 2.3 years, and 2948 subcohort members of The Netherlands Cohort Study on diet and cancer. Adjusted incidence rate ratios and 95% confidence intervals were computed for colon and rectal cancer and for K-ras mutation status subgroups. Total fresh meat, most types of fresh meat and fish were not associated with colon or rectal cancer, neither overall nor with K-ras mutation status. However, several weak associations were observed for tumours with a wild-type K-ras, including beef and colon tumours, and an inverse association for pork with colon and rectal tumours; for meat products, an increased association was observed with wild-type K-ras tumours in the colon and possibly with G4A transitions in rectal tumours.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

et al. 2005

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“…Previously, MNU has been shown to induce G : C to A : T mutations in N-ras codon 61 in rat mammary tumors (Zarbl et al, 1985;Cha et al, 1994) and in K-ras codon 12 (GGT) in mouse lymphomas (Corominas et al, 1991). Thus, in mice, there should be a correlation between the number and type of mutations induced by MNU and activation of K-ras in the resulting lymphomas.…”

mentioning

confidence: 98%

Mice over-expressing human O6alkylguanine-DNA alkyltransferase selectively reduce O6methylguanine mediated carcinogenic mutations to threshold levels after N-methyl-N-nitrosourea

1999

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“…A large body of evidence indicates that several factors, including endogenous metabolites and exogenous carcinogen compounds can induce DNA damage (Zarbl et al, 1985). The nature and the location of the mutational change within the TP53 gene di er greatly among tumors of di erent histological type which may be a re¯ection of some DNA genotoxic agents (Greenblatt et al, 1994).…”

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confidence: 99%

TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis

Anta

Jassem²,

Rosell

et al. 1997

Oncogene

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Inactivation of TP53 tumor suppressor gene is the most frequent molecular alteration in NSCLC, involving up to 60% of cases. Furthermore, TP53 mutational spectrum is related to the type of mutagen exposure, as well as racial and/or diet di erences. Nearly 95% of TP53 perturbations a ect codons included within exons 5 ± 8 which encode for almost the entire DNA-binding domain. In this study we addressed the possible prognostic value of the molecular alterations identi®ed in exons 5 ± 8 of the TP53 gene in DNAs from 151 para n-embedded NSCLC sections corresponding to 59 Spanish and 92 Polish stage I-IIIA resected patients. PCR/single-strand conformation polymorphism (SSCP) analysis revealed that the occurrence of TP53 exon 5 ± 8 mutations was 17/59 (29%) in the Spanish cohort and 17/92 (18%) in the Polish group. However, when DNA sequencing analysis was performed, these frequencies were reduced because of the presence of SSCP-false positive, intronic and silent mutations and polymorphisms. Fifteen of the 59 Spanish NSCLC tumors (25%) harbored TP53 mutations a ecting exons 5 ± 8 coding sequences, whereas only 12 of 92 Polish neoplasms (13%) contained alterations in the central hydrophobic region of p53. Our results indicate that the occurrence of TP53 mutations a ecting exon 5 ± 8 coding sequences in some European NSCLC populations may be lower than previously reported, and that the TP53 mutational patterns of these cohorts di er somewhat. The Spanish NSCLC patients contained missense mutations (9/59, 15%) and a relatively high percentage of null mutations (5/59, 8%) while the Polish patients mostly harbored missense mutations (9/92, 10%) and only one tumor contained a null type (1/92, 1%). Moreover, most TP53 missense mutations in the Spanish group were located outside the conserved regions, whereas the same mutations in the Polish group a ected conserved amino acids. Furthermore, the Polish patients harbored a high percentage of G?A transitions (most of them at non-CpG sites), while G?T transversions were predominant in the Spanish group. Our ®ndings suggest that there may be di erent racial or exogenous factors in these two populations which may help to explain both the distinct TP53 mutational pattern and the lower frequency obtained in the Polish group. The presence of missense mutations did not confer a worse clinical outcome in these subsets of NSCLC patients. However, patients whose tumors contained null TP53 gene mutations had a 5 month median disease-free survival time in contrast with 42 months in those patients without mutations (P=0.008). These ®ndings suggest that loss of p53 function may enhance tumor progression in NSCLC patients independently of whether dominant negative TP53 missense mutations are present.

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Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats

Cited by 786 publications

References 21 publications

Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

Mice over-expressing human O6alkylguanine-DNA alkyltransferase selectively reduce O6methylguanine mediated carcinogenic mutations to threshold levels after N-methyl-N-nitrosourea

TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis

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