PT  - JOURNAL ARTICLE
AU  - Cabelof, Diane C.
AU  - Ikeno, Yuji
AU  - Nyska, Abraham
AU  - Busuttil, Rita A.
AU  - Anyangwe, Njwen
AU  - Vijg, Jan
AU  - Matherly, Larry H.
AU  - Tucker, James D.
AU  - Wilson, Samuel H.
AU  - Richardson, Arlan
AU  - Heydari, Ahmad R.
TI  - Haploinsufficiency in DNA Polymerase β Increases Cancer Risk with Age and Alters Mortality Rate
AID  - 10.1158/0008-5472.CAN-06-1177
DP  - 2006 Aug 01
TA  - Cancer Research
PG  - 7460--7465
VI  - 66
IP  - 15
4099  - http://cancerres.aacrjournals.org/content/66/15/7460.short
4100  - http://cancerres.aacrjournals.org/content/66/15/7460.full
SO  - Cancer Res2006 Aug 01; 66
AB  - This study uses a base excision repair (BER)–deficient model, the DNA polymerase β heterozygous mouse, to investigate the effect of BER deficiency on tumorigenicity and aging. Aged β-pol+/− mice express 50% less β-pol transcripts and protein (P < 0.05) than aged β-pol+/+ mice, showing maintenance of the heterozygous state over the life span of the mouse. This reduction in β-pol expression was not associated with an increase in mutation rate but was associated with a 100% increase in the onset of hypoploidy. Aged β-pol+/− mice exhibited a 6.7-fold increase in developing lymphoma (P < 0.01). Accordingly, 38% of β-pol+/− mice exhibited lymphoid hyperplasia, whereas none of the β-pol+/+ exhibited this phenotype. β-pol+/− mice were also more likely to develop adenocarcinoma (2.7-fold increase; P < 0.05) and more likely to develop multiple tumors, as 20% of the β-pol+/− animals died bearing multiple tumors compared with only 5% of the β-pol+/+ animals (P < 0.05). In spite of accelerated tumor development, no gross effect of β-pol heterozygosity was seen with respect to life span. However, the survival curves for the β-pol+/+ and β-pol+/− mice are not identical. A maximum likelihood estimation analysis showed a modest but significant (P < 0.05) acceleration of the age-dependent mortality rate in β-pol+/− mice. Thus, the β-pol+/− mouse represents a model in which mortality rate and tumor development are accelerated and provides evidence supporting the role of genomic maintenance in both aging and carcinogenesis. (Cancer Res 2006; 66(15): 7460-5) ©2006 American Association for Cancer Research.