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Radiation Oncology
Published in: Radiation Oncology 1/2011

Open Access 01-12-2011 | Research

Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

Authors: Jufang Wang, Fengtao Su, Lubomir B Smilenov, Libin Zhou, Wentao Hu, Nan Ding, Guangming Zhou

Published in: Radiation Oncology | Issue 1/2011

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Abstract

Background

Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity.

Methods

Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation.

Results

Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways.

Conclusions

The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.
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Metadata
Title
Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity
Authors
Jufang Wang
Fengtao Su
Lubomir B Smilenov
Libin Zhou
Wentao Hu
Nan Ding
Guangming Zhou
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2011
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-6-96

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