This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Furan induces high incidences of cholangiocarcinoma and hepatocellular carcinomas in rats, but the mechanisms of tumor formation by furan in rodents are not well understood. The objective of this study is to assess DNA and protein binding after single oral administration of [3,4-14C]-furan to rats at doses close to human exposure. Thereby, information will be obtained on dose-response and molecular mechanisms of furan carcinogenicity as a basis for risk assessment of human furan exposures with food. This study WP 1.1 is designed to establish whether furan is genotoxic or if carcinogenicity may be a consequence of toxicity induced by protein-binding. Therefore DNA and proteins isolated from liver will be analysed to determine their 14C-content. Rats will be used due to their high sensitivity and the specific pathology induced by furan in this species.
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