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National Academy of Sciences, Proceedings of the National Academy of Sciences, 10(98), p. 5770-5775, 2001

DOI: 10.1073/pnas.081082898

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Carcinogen-specific induction of genetic instability

Journal article published in 2001 by Alberto Bardelli, Daniel P. Cahill, Gabi Lederer, Michael R. Speicher ORCID, Kenneth W. Kinzler, Bert Vogelstein, Christoph Lengauer
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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 .