An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer.
Fischer rat embryo fibroblasts subjected to temporary anoxia followed by an aerobic recovery period show genomic instability in the form of highly elevated CAD gene amplification rates. As revealed by flow cytometric analysis this is associated with DNA breakage in vivo, followed by repair during the recovery period. Such genomic instability parallels expression of a M(r) 29,000/31,000 endonuclease; this enzyme requires no added divalent metal ion and has a pH optimum of about 6.5. The same endonuclease was found to be expressed within healing wounds and in four of ten human colorectal cancers but was not seen in eight normal colorectal tissue samples. Our results indicate that DNA breakage resulting from endogenous endonuclease activity can have a substantial effect in modulating genomic instability.
Russo
C A
CA
Roswell Park Cancer Institute, Buffalo, New York 14263.
Weber
T K
TK
Volpe
C M
CM
Stoler
D L
DL
Petrelli
N J
NJ
Rodriguez-Bigas
M
M
Burhans
W C
WC
Anderson
G R
GR
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D005784:Gene Amplification; D016678:Genome; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics; D008970:Molecular Weight; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344
D004273:DNA, Neoplasm; D004720:Endonucleases