Use of organ cultures in human risk assessment: Comparisons of benzo[a]pyrene-DNA adducts in mouse and human skin.
Human and mouse skin explant systems have been developed as models that qualitatively mimic the genotoxic metabolism in vivo of benzo[a]pyrene, a representative carcinogenic polycyclic aromatic hydrocarbon. High-performance liquid chromatography profiles of DNA adducts isolated from CD-1 mouse skin treated with [(3)H]benzo[a]pyrene either in vivo or in vitro were qualitatively very similar. (32)P-Post-radiolabelling and thin-layer chromatography analysis of these DNA adducts also yielded profiles that were qualitatively similar both in vivo and in vitro. The presence of a component that did not appear to correspond to those detected by direct labelling was also revealed by (32)P-postlabelling. These approaches have been applied in order to develop valid risk models for chemical carcinogens, and in addition, to provide valuable reference standards for the detection of human genotoxic metabolism. Thus the coupling of human skin explant systems with (32)P-postlabelling techniques has provided a direct in vitro model for the prospective detection of human carcinogens.
Watson
W P
WP
Shell Research Ltd, Sittingbourne Research Centre, Sittingbourne, Kent ME9 8AG, England.
Smith
R J
RJ
Huckle
K R
KR
Wright
A S
AS