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Proc Natl Acad Sci U S A. 2001 May 8;98(10):5770-5. Epub 2001 Apr 10.

Carcinogen-specific induction of genetic instability.

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  • 1The Johns Hopkins Oncology Center, Howard Hughes Medical Institute, and Graduate Program in Human Genetics and Molecular Biology, 1650 Orleans Street, Baltimore, MD 21231, USA.


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.

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