Carcinogens induce reversion of the mouse pink-eyed unstable mutation.
Deletions and other genome rearrangements are associated with carcinogenesis and inheritable diseases. The pink-eyed unstable (pun) mutation in the mouse is caused by duplication of a 70-kb internal fragment of the p gene. Spontaneous reversion events in homozygous pun/pun mice occur through deletion of a duplicated sequence. Reversion events in premelanocytes in the mouse embryo detected as black spots on the gray fur of the offspring were inducible by the carcinogen x-rays, ethyl methanesulfonate, methyl methanesulfonate, ethyl nitrosourea, benzo[a]pyrene, trichloroethylene, benzene, and sodium arsenate. The latter three carcinogens are not detectable with several in vitro or in vivo mutagenesis assays. We studied the molecular mechanism of the carcinogen-induced reversion events by cDNA analysis using reverse transcriptase-PCR method and identified the induced reversion events as deletions. DNA deletion assays may be sensitive indicators for carcinogen exposure.
Schiestl
R H
RH
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. schiestl@mbcrr.harvard.edu
Aubrecht
J
J
Khogali
F
F
Carls
N
N
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002352:Carrier Proteins; D006200:Hair Color / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009152:Mutagenicity Tests / Q000379:methods*; D011995:Recombination, Genetic / Q000187:drug effects; D017384:Sequence Deletion
D002273:Carcinogens; D002352:Carrier Proteins; D008565:Membrane Proteins; C076239:P protein, mouse