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PMID: 11296254 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Carcinogen-specific induction of genetic instability.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 10 ·2001-05-08 ·Pages 5770-5

Bardelli A, Cahill DP, Lederer G, Speicher MR, Kinzler KW, Vogelstein B, Lengauer C

Abstract

It has been proposed recently that the type of genetic instability in cancer cells reflects the selection pressures exerted by specific carcinogens. We have tested this hypothesis by treating immortal, genetically stable human cells with representative carcinogens. We found that cells resistant to the bulky-adduct-forming agent 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) exhibited a chromosomal instability (CIN), whereas cells resistant to the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) exhibited a microsatellite instability (MIN) associated with mismatch repair defects. Conversely, we found that cells purposely made into CIN cells are resistant to PhIP, whereas MIN cells are resistant to MNNG. These data demonstrate that exposure to specific carcinogens can indeed select for tumor cells with distinct forms of genetic instability and vice versa.

MeSH Terms
Blotting, Western Carcinogens/toxicity Cell Line Imidazoles/toxicity In Situ Hybridization, Fluorescence Methylnitronitrosoguanidine/toxicity Microsatellite Repeats/drug effects
Chemicals
Carcinogens Imidazoles Methylnitronitrosoguanidine 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bardelli A
The Johns Hopkins Oncology Center, Howard Hughes Medical Institute, and Graduate Program in Human Genetics and Molecular Biology, 1650 Orleans Street, Baltimore, MD 21231, USA.
Cahill D P
Lederer G
Speicher M R
Kinzler K W
Vogelstein B
Lengauer C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.081082898
Published
2001-05-08
Epub
2001-00-10
Pages
5770-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC33288
Subset
IM
Grants
NCI NIH HHS · P50 CA062924 · United States
NCI NIH HHS · R37 CA043460 · United States
NCI NIH HHS · CA 43460 · United States
NCI NIH HHS · CA 62924 · United States
Corrections
CommentIn
PMID: 11344279
External Links
PubMed source DOI: 10.1073/pnas.081082898 PMC Full Text View journal details
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