Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whole cell preparations derived from collagenase-treated rat liver were cocultivated overnight with stationary (non-shaking) cultures of L5178Y/TK+/- cells in the presence of 8 different chemicals selected as representative aromatic amine, polycyclic hydrocarbon, or nitrosamine procarcinogens. When tested in the presence of hepatocytes, 2-aminoanthracene, 2-aminofluorene, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodipropylamine, 3-methylcholanthrene, and benzo[a]pyrene all produced substantial dose-dependent increases in trifluorothymidine-resistant variants compared to solvent controls after 20 h total exposure time. Only N-nitrosodipropylamine (DPrN) and N-nitrosodiethylamine (DEN) produced any dose-related mutagenic activity in similar experiments where hepatocytes were omitted; however, the response for the DPrN was quite variable at high doses in the absence of hepatocytes and the mutagenic response for the DEN was consistently enhanced at all dose levels by the presence of hepatocytes. Benzanthracene was not active in the presence of whole hepatocytes, even when tested with cells from a rat pretreated 24 h earlier with 20 mg/kg benzanthracene. Excepting benzanthracene, these data suggest that rat hepatocytes can be used to active 3 types of procarcinogens to mutagens in the L5178Y/TK gene mutation assay.
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PMID:The activation of procarcinogens to mutagens by cultured rat hepatocytes in the L5178Y/TK mutation assay. 682 44

Polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs have been identified widely in occupational and environmental pollution, such as diesel engine emissions and other combustion products. In most cases, hepatic biotransformation is involved in converting these chemicals to their carcinogenic metabolites. It has been demonstrated that isolated hepatocytes possess substantial amounts of the enzymes responsible for metabolizing xenobiotics and are therefore a convenient model for studying chemicals that require activation to exert their carcinogenic effects. In this study, rat hepatocytes were isolated by collagenase digestion and then exposed to benzo[a]pyrene (B) [a]P), benzo[a]anthracene (B[a]A), 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-DNP) at different doses and/or times so that DNA adducts levels, as measured with the (32)P-postlabelling technique, could be compared. Each of the four compounds tested induced significant increases of total DNA adducts with clear dose-related responses. One or more individual adducts were identified as major adducts for each compound. Time-related increases of DNA adducts were also observed from 1 to 4 hr of incubation. Greater amounts of DNA adducts were induced by B[a]P or 1,6-DNP than by B[a]A or 1-NP, with potency being in the order 1,6-DNP > B[a]P > 1-NP B[a]A. These results demonstrate that freshly isolated hepatocytes can be used as an effective in vitro system for the detection of DNA adducts using (32)P-postlabelling, and have shown 1,6-DNP to be the most potent of the tested constituents of diesel emissions.
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PMID:Comparison of DNA adduct induction in vitro by PAHs and nitro-pahs in freshly isolated rat hepatocytes. 2065 Feb 52