Mouse Models for Xeroderma Pigmentosum Group A and Group C Show Divergent Cancer Phenotypes

Abstract

The accumulation of DNA damage is a slow but hazardous phenomenon that may lead to cell death, accelerated aging, and cancer.

Nucleotide Excision Repair and Cancer

“…The spontaneous survival characteristics of Xpc mice in a pure genetic C57BL/6J background together with their related wild type littermates were also investigated. Xpc mice showed a significant decrease in survival, again exhibited a significant increase in lung and liver tumors and an increased mutation accumulation in these tissues compared to wild type mice (Melis et al, 2008). Here, Xpc mice showed a divergent tumor spectrum from Xpa mice in the same genetic C57BL/6J background.…”

“…A small (but not significant) increase in lung tumors was also observed (6.6% of the Xpa mice) (Melis et al,2008). Correspondingly, mutation accumulation in the C57BL/6J Xpa mice was significantly increased during survival compared to wild type mice in liver, implicating an Xpa repair defect and subsequent mutation induction in carcinogenesis (Melis et al,2008). Like human XP-A patients, Xpa mice appeared predisposed to skin cancer after UV light exposure to shaved dorsal skin of the mice (de Vries et al,1995;Tanaka et al,2001).…”

“…In a pure genetic background a significant increase in liver tumors was observed (10%). A small (but not significant) increase in lung tumors was also observed (6.6% of the Xpa mice) (Melis et al,2008). Correspondingly, mutation accumulation in the C57BL/6J Xpa mice was significantly increased during survival compared to wild type mice in liver, implicating an Xpa repair defect and subsequent mutation induction in carcinogenesis (Melis et al,2008).…”

“…The additional increase in lung tumor development in two independent spontaneous survival studies indicate XPC is involved in other pathways besides NER. A corresponding strong increase in mutational load during aging was found in lungs of the C57BL/6J Xpc mice, which was not the case in Xpa mice (Melis et al,2008). Uehara et al have shown that enhanced spontaneous age-related mutation accumulation in Xpc mice is tissue dependent.…”

“…Overview of spontaneous phenotypes of NER-deficient mouse models background for this and other mouse models made it harder to investigate the underlying cause of the phenotypic responses in these mice. An Xpa mouse model in a pure genetic www.intechopen.com C57BL/6J background more recently was investigated (Melis et al,2008). C57BL/6J mice showed a low baseline tumor response and appear therefore suitable for studying mutagenesis and tumorigenesis.…”