ANTIMUTAGENIC ACTIVITY AND METABOLIC TRANSFORMATION OF RANUNCULIN BY RAT LIVER MICROSOMES

Ranunculin (RAN) was shown to be an antimutagenic agent selectively against mitomycin C (MMC) or methyl methane sulfanate (MMS) treated Salmonella typhimminum TA₁₀₀/TA₁₀₂. It decreased the formation of micronucleus of MMC induced polychromatic erythrocytes (PEC) from 46±9.2% to 20±6% in mice. The inhibition of RAN on the incorporation of ³H-TdR into DNA disappeared after incubation with rat liver microsomes and cytoplasm since RAN was found to be metablized by rat liver microsomes in vitro, resulting in a new absorbance peak at 258 nm, determined by RP-HPLC. The data show that RAN may have both antimutagen and antitumor activity, but the latter action may disappear by metabolic transformation.