Comparative activity of human carcinogens and NTP rodent carcinogens in the mouse bone marrow micronucleus assay: an integrative approach to genetic toxicity data assessment

Environmental Health Perspectives
H Tinwell, J Ashby

Abstract

The mouse bone marrow micronucleus (MN) assay holds a key position in all schemes for detecting potential human carcinogens and mutagens. It was therefore of concern when Shelby et al. reported that only 5 of 25 rodent carcinogens defined by the U.S. NTP were positive in the assay. Further, each of these positive responses was weak and indistinguishable from the 4 positive responses observed among the 24 NTP noncarcinogens tested. To focus these findings, the activity in the MN assay of 26 human carcinogens, 6 reference rodent genotoxins, and the 9 NTP chemicals positive in the MN assay have been displayed in a common format. This involved plotting the minimum positive dose level (expressed as mumole/kilogram) and the maximum fold-increase in micronucleated polychromatic erythrocytes frequency observed at any dose level. By displaying the high sensitivity of the micronucleus assay to the reference human and rodent genotoxins, this analysis emphasizes the weakness in the MN assay responses given by the NTP carcinogens reported by Shelby et al. This, in turn, poses questions about the intrinsic hazard of this selection of NTP rodent carcinogens. Using fotemustine and vitamin C as models of a toxic and a nontoxic chemical known to...Continue Reading

References

Nov 1, 1979·Mutation Research·A LéonardL Fabry
Jan 1, 1991·Environmental and Molecular Mutagenesis·H Tinwell, J Ashby
Jun 1, 1991·Mutation Research·J AshbyH Tinwell
Nov 1, 1990·Mutagenesis·F Z ArrouijalD Marzin
Jun 1, 1990·Mutation Research·S SutouY Mitsui
Apr 1, 1989·Mutation Research·J Ashby
Jan 1, 1989·Environmental and Molecular Mutagenesis·Y SuzukiH Shimizu
Jan 1, 1988·Environmental and Molecular Mutagenesis·J AshbyR Albanese
Jan 1, 1988·Mutation Research·M D Shelby
Sep 1, 1984·Mutation Research·B L HarperM S Legator
Oct 1, 1983·Mutation Research·M T King, D Wild
Jun 1, 1984·Toxicology Letters·B B GollapudiA K Sinha
Jul 1, 1981·Mutation Research·P GilbertM Mercier
Oct 1, 1982·Mutation Research·B E MatterW Suter
Jan 1, 1980·Mutation Research·C L Chrisman, A P Baumgartner
Jun 1, 1994·Mutation Research·M HayashiH Shimada
Jan 1, 1994·Mutagenesis·J Ashby, R W Tennant
Jan 1, 1994·Toxicology and Applied Pharmacology·M L CunninghamJ R Bucher
Jan 1, 1993·Environmental and Molecular Mutagenesis·M D ShelbyR R Tice

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Citations

Oct 24, 2001·Environmental Health Perspectives·A R Cunningham, H S Rosenkranz
Sep 2, 2014·Toxicology Mechanisms and Methods·Pınar Erkekoglu, Belma Kocer-Gumusel

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