Production of unscheduled DNA synthesis in rodent hepatocytes in vitro, but not in vivo, by 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX)

• Published in: Mutation research Vol. 373; no. 1; p. 67
• Main Authors: Nunn, J W, Davies, J E, Chipman, J K
• Format: Journal Article
• Language: English
• Published: Netherlands 03.01.1997
• Subjects: Administration, Oral; Animals; Buthionine Sulfoximine - pharmacology; Cells, Cultured; DNA - biosynthesis; DNA Damage - drug effects; DNA Repair - drug effects; Dose-Response Relationship, Drug; Furans - pharmacology; Glutathione - metabolism; Humans; Liver - cytology; Liver - drug effects; Male; Mice; Mice, Inbred BALB C; Mutagens - pharmacology; Rats; Rats, Wistar
• ISSN: 0027-5107
• DOI: 10.1016/S0027-5107(96)00190-X

Incubation of both rat and mouse hepatocytes with 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) in vitro resulted in a dose-dependent increase in unscheduled DNA synthesis (UDS) at sub-cytotoxic concentrations (1-10 microM MX; 20 h incubation). Depletion of glutathione stores by pre-treatment of rat hepatocytes with buthionine sulfoximine did not result in a significant increase in UDS produced by MX. In contrast, MX did not induce UDS in mouse hepatocytes ex vivo either 3 or 16 h following administration of a single oral dose of 100 mg/kg MX. Despite the ability of MX to produce repairable DNA damage, restricted access of MX to the liver may prevent a measurable UDS response in vivo.