Objectives of Project: 1. Determine if non-cytotoxic doses of furan induce liver neoplasms in female B6C3F1 mice. Background and Significance: Furan is the parent structure of a large class of naturally occurring and synthetic compounds. Furan is hepatocarcinogenic and hepatotoxic, but not mutagenic or directly DNA reactive, and thus is considered a model agent for studying the dose-response characteristics and mechanisms of action of cytotoxic carcinogens. High dose levels of furan (>8.0 mg/kg) have previously been shown to induce necrosis, apoptosis, inflammation, and increased regenerative hepatocyte cell replication. Study results may have important implications for other rodent carcinogens that are believed to operate via a similar mode of action. Achievements and Future Plans: 1. Necropsy and microscopic evaluations demonstrated an increased tumor incidence and multiplicity, as well as decreased tumor latency in the 4.0 and 8.0 mg/kg furan-exposed mice but not in mice at lower doses. This study provides strong experimental evidence for the demonstration of the relationship between dose, cytotoxicity, compensatory cell growth, and tumor induction for a model hepatic cytotoxic carcinogen. Future Plans: Final analysis of data and publication of results.
