Carcinogen-specific induction of genetic instability

Alberto Bardelli, Daniel P. Cahill, Gabi Lederer, Michael R. Speicher, Kenneth W. Kinzler, Bert Vogelstein, Christoph Lengauer

Research output: Contribution to journalArticle

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 (PhlP) 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 PhlP, 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.

Original languageEnglish (US)
Pages (from-to)5770-5775
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number10
DOIs
StatePublished - May 8 2001

ASJC Scopus subject areas

  • General

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