Targeting Reactive Nitrogen Species Suppresses Hereditary Pancreatic Cancer

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2017 Jun 21

PMID 28630313

Citations 8

Authors

Mo Li

Qian Chen

Teng Ma

Xiaochun Yu

Affiliations

Soon will be listed here.

Abstract

Germline mutation of BRCA2 induces hereditary pancreatic cancer. However, how BRCA2 mutation specifically induces pancreatic tumorigenesis remains elusive. Here, we have examined a mouse model of Brca2-deficiency-induced pancreatic tumors and found that excessive reactive nitrogen species (RNS), such as nitrite, are generated in precancerous pancreases, which induce massive DNA damage, including DNA double-strand breaks. RNS-induced DNA lesions cause genomic instability in the absence of Brca2. Moreover, with the treatment of antioxidant tempol to suppress RNS, not only are DNA lesions significantly reduced, but also the onset of pancreatic cancer is delayed. Thus, this study demonstrates that excess RNS are a nongenetic driving force for Brca2-deficiency-induced pancreatic tumors. Suppression of RNS could be an important strategy for pancreatic cancer prevention.

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