the information about menadione

Menadione promotes hepatic biosynthesis of coagulation factors. The carcinogenic potential of menadione was determined by DC polarography in strictly anhydrous N,N-dimethylformamide (DMF) in the presence of α-lipoic acid. Superoxide anion formation was measured after incubation of menadione rat lung, liver and kidney microsomes with menadione. Potential genotoxicity of menadione was investigated using unscheduled DNA synthesis (UDS) and alkaline elution assays. The carcinogenic potential parameter for menadione on alpha was 0.0025, indicating that menadione had no carcinogenic activity. When menadione is incubated with microsomes, superoxide anion is generated in a concentration- and time-dependent manner. Menadione is cytotoxic at concentrations above 20 nmol/mL in mammalian cells (A 549) for alkaline elution and UDS assays. Cytotoxicity of menadione was reduced using the S9 pooled (metabolically activated) fraction. Menadione was genotoxic in the UDS test in the absence of metabolic activation in the concentration range above 20 nmol/mL. In the presence of metabolic activation, menadione-induced DNA damage and repair are greatly reduced. Treatment of A 549 lung cells with 4-nitroquinoline-N-oxide (NQO) in the absence and presence of metabolic activation resulted in significant formation of DNA single-strand breaks. Treatment of A549 lung cells with menadione in the absence of S9 mixture resulted in the formation of DNA single-strand breaks. In the presence of metabolic activation, menadione does not cause significant DNA strand break formation. Menadione-induced DNA repair in A 549 cells is concentration-, time-, and temperature-dependent. Unscheduled DNA (UDS) synthesis (repair) measurements after treatment with NQO and menadione in the absence of S9 mixture produced a strong UDS response. Taken together, the results of these studies suggest that NQO and menadione have mutagenic potential. These results suggest that menadione undergoes a redox cycle to form reactive oxygen species that lead to DNA damage and repair, but has no carcinogenic potential

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