8-Hydroxyguanosine repair is defective in some microsatellite stable colorectal cancer cells.
Mutator phenotypes are involved in the carcinogenesis of some cancers, e.g., defects in mismatch repair produce a mutator phenotype that drives carcinogenesis and causes microsatellite instability in hereditary nonpolyposis colon cancers and some sporadic colorectal cancers (CRC). Less understood, however, is the potential role of mutator phenotypes in microsatellite stable (MSS) CRC carcinogenesis. A novel transversion mutator phenotype was reported recently in an MSS CRC cell line. We hypothesized that 8-hydroxyguanosine could be involved and found elevations in 5 of 15 (33%) MSS CRC cell lines analyzed. Repair of an adenine*8-hydroxyguanosine mispair was functionally defective in the same five cell lines. The human MutY homologue transcript and MutY homologue protein levels were also decreased. These findings may reflect a MSS mutator phenotype contributing to the development of CRC.
Parker
Antony R
AR
Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
O'Meally
Robert N
RN
Oliver
Dwight H
DH
Hua
Li
L
Nelson
William G
WG
DeWeese
Theodore L
TL
Eshleman
James R
JR
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D045647:DNA Glycosylases; D004260:DNA Repair; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D005656:Fungal Proteins; C118806:MTH1 protein, S cerevisiae; D008565:Membrane Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase