CGH analysis of radon-induced rat lung tumors indicates similarities with human lung cancers

Dano, Laurent; Guilly, Marie-Noëlle; Muleris, Martine; Morlier, Julien; Altmeyer, Sandrine; Vielh, Philippe; El‐Naggar, Adel K.; Monchaux, G.; Dutrillaux, Bernard; Chevillard, Sylvie

doi:10.1002/1098-2264(2000)9999:9999<000::aid-gcc1000>3.0.co;2-0

Cited by 5 publications

(1 citation statement)

References 36 publications

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“…Dano et al developed a model of radon-induced rat lung tumours using comparative genomic hybridisation, and found frequent losses in chromosomes 4q12-21, 5q11-33, 15q and 19q, which are homologous to human chromosomes. These regions contain tumor suppressor genes and proto-oncogenes such as MET, CDKN2A, MTS2, FHIT, RB1 and MYC [50]. The genetic similarities between rat and human lung cancer may suggest common underlying carcinogenic mechanisms in both species.…”

Section: Preclinical Evidencementioning

confidence: 99%

Radon and Lung Cancer: Current Trends and Future Perspectives

Riudavets

Herreros

Besse

et al. 2022

Cancers

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Lung cancer is a public health problem and the first cause of cancer death worldwide. Radon is a radioactive gas that tends to accumulate inside homes, and it is the second lung cancer risk factor after smoking, and the first one in non-smokers. In Europe, there are several radon-prone areas, and although the 2013/59 EURATOM directive is aimed to regulate indoor radon exposition, regulating measures can vary between countries. Radon emits alpha-ionizing radiation that has been linked to a wide variety of cytotoxic and genotoxic effects; however, the link between lung cancer and radon from the genomic point of view remains poorly described. Driver molecular alterations have been recently identified in non-small lung cancer (NSCLC), such as somatic mutations (EGFR, BRAF, HER2, MET) or chromosomal rearrangements (ALK, ROS1, RET, NTRK), mainly in the non-smoking population, where no risk factor has been identified yet. An association between radon exposure and oncogenic NSCLC in non-smokers has been hypothesised. This paper provides a practical, concise and updated review on the implications of indoor radon in lung cancer carcinogenesis, and especially of its potential relation with NSCLC with driver genomic alterations.

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Section: Preclinical Evidencementioning

confidence: 99%

Radon and Lung Cancer: Current Trends and Future Perspectives

Riudavets

Herreros

Besse

et al. 2022

Cancers

View full text Add to dashboard Cite

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Comparative genomic hybridization analysis of N‐methyl‐N′‐nitrosoguanidine‐induced rat gastrointestinal tumors discloses a cytogenetic fingerprint

Corso

Parry

2004

Environ and Mol Mutagen

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Exposure to N-nitroso compounds is thought to play a key role in the development of gastric cancer in humans. The alkylating agent N-methyl-N'-nitrosoguanidine (MNNG) is carcinogenic in a number of animal models and its preferential target tissue is the gastrointestinal (GI) tract. The genetic synteny among rats and humans makes the rat a useful model for induced tumorigenesis. However, because of the limited availability of genetic information, cytogenetic and molecular studies are rarely performed in the rat. We report an investigation of eight MNNG-induced rat gastric tumors by comparative genomic hybridization (CGH). The tumors were from forestomach (induced by a single dose of MNNG) and from pylorus (induced by chronic exposure). CGH identified a genetic fingerprint of chromosomal imbalances common to the two types of the tumors. Frequent gains were observed at 9q11-q12, 15q22-25, and Xq11-q12. Forestomach carcinomas were also characterized by gains in 7q11-q12, 20q13, and Yq12. Homology studies between the rat and human genomes indicate the presence of genes within these regions with potential relevance to tumorigenesis in the GI tract. Our findings provide new insights into the location of genes involved in MNNG-induced gastric cancer initiation and/or progression in the rat.

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Tumor cells can escape DNA‐damaging cisplatin through DNA endoreduplication and reversible polyploidy

Puig

Guilly

Bouchot

et al. 2008

Cell Biology International

237

216

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Cancer chemotherapy can induce tumor regression followed, in many cases, by relapse in the long-term. Thus this study was performed to assess the determinants of such phenomenon using an in vivo cancer model and in vitro approaches. When animals bearing an established tumor are treated by cisplatin, the tumor initially undergoes a dramatic shrinkage and is characterized by giant tumor cells that do not proliferate but maintain DNA synthesis. After several weeks of latency, the tumor resumes its progression and consists of small proliferating cells. Similarly, when tumor cells are exposed in vitro to pharmacological concentrations of cisplatin, mitotic activity stops initially but cells maintain DNA duplication. This DNA endoreduplication generates giant polyploid cells that then initiate abortive mitoses and can die through mitotic catastrophe. However, many polyploid cells survive for weeks as non-proliferating mono- or multi-nucleated giant cells which acquire a senescence phenotype. Prolonged observation of these cells sheds light on the delayed emergence of a limited number of extensive colonies which originate from polyploid cells, as demonstrated by cell sorting analysis. Theses colonies are made of small diploid cells which differ from parental cells by stereotyped chromosomal aberrations and an increased resistance to cytotoxic drugs. These data suggest that a multistep pathway, including DNA endoreduplication, polyploidy, then depolyploidization and generation of clonogenic escape cells can account for tumor relapse after initial efficient chemotherapy.

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CGH analysis of radon-induced rat lung tumors indicates similarities with human lung cancers

Cited by 5 publications

References 36 publications

Radon and Lung Cancer: Current Trends and Future Perspectives

Radon and Lung Cancer: Current Trends and Future Perspectives

Comparative genomic hybridization analysis of N‐methyl‐N′‐nitrosoguanidine‐induced rat gastrointestinal tumors discloses a cytogenetic fingerprint

Tumor cells can escape DNA‐damaging cisplatin through DNA endoreduplication and reversible polyploidy

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