Phytomedicine Vol. 4/1995, pp. 319-322 © 1995 by Gustav Fischer Verlag, Stuttgart : Jena . New York Investigation of genotoxic effects of the anti-asthmatic and anti-inflammatory drugs Apocynin and Acetosyringe- nin in the Salmonella typhimurium mutagenicity assay and the SeE-test with human lymphocytes S. PFUHLER1, P. STEHRER-SCHMID1, W. DORSCH2, H. WAGNER3 and H. U. Wolf 1 1 Abteilung Pharmakologie und Toxikologie, Universitar Ulm, Albert-Einstein-Allee 11, D-89081 Ulm (FRG) 2 Aidenbachstr. 118, D-81397 Miinchen (FRG) 3 Institut fur Pharmazeutische Biologie, Ludwig-Maximilians-Universirar, Karlsstr. 29, D-80033 Miinchen (FRG) Summary We examined the possible genotoxicity of the recently isolated or developed anti-as thmatic and anti-inflammatory substa nces Apocynin (CAS 498-02-2) and Acetosyringeni n (CAS 2478-38-8) using short term test systems. Apocynin is a constituent of Picrorhiza kurroa, a plant from the Himalaya region. Acetosyringenin is its methoxylated synthetic derivative. The test systems used were the Salmonella typhimurium mutagenicity assay (Ames test) with the tester strains TA 97, TA 98, TA 100, and TA 102, and the sister chromatid exchange assay (SCE-Test) performed with human peripheral lymphocytes. The genetic endpoints covered by these test systems are the induction of gene mutations and the induction of SCEs, which is inter- preted as an indicator for DNA-damaging properties of the test compound. The results obtained with Apocynin and Acetosyringenin do not demonstrate genotoxic activ- ities of these compounds regarding the investigated endpoints. Key words: Apocynin, Acetosyringenin, genotoxicity, Salmonella typhimurium mutagenicity assay, sister chromatid exchange test, human peripheral lymphocytes. Introduction The anti-asthmatic and anti-inflammatory drugs that were investigated in this study were isolated from a plant which is applied in the traditional medicine of its home re- gion. The phenol derivative 4-Hydroxy-3-methoxy-ace- tophenone (trivial name Apocynin, [1] former name Ace- tovaniIlone) is a constituent of root extracts of the medical herb Picrorhiza kurroa Royle ex Benth. - a small plant with tuberous roots that occurs naturally in the Himalaya region in heights above 3 000 m. Picrorhiza kurroa has been exten- sively used in oriental medicine for a variety of conditions like lung and liver disease, fever, rheumatic disease etc. Pic- rorhiza kurroa root powder was found to inhibit histamine release in vitro (Dorsch and Wagner, 1991). The anti-in- flammatory activity of Apocynin is based on the inhibition of the release of mediators of inflammation such as throm- boxane A 2 (Engels, Renirie, t'Hart et aI., 1992), and also the inhibition of neutrophil superoxide production (t'Hart, Simons, Knaan -Shanzer et aI., 1990). 3,5-Dimethoxy-4-hy- droxy-acetophenone (Acetosyringenin, [2] former name Acetosyringone), a methoxylated semisynthetic derivative of Apocynin, has a high anti-asthmatic activity (Stuppner and Wagner, 1989; Stuppner, Dorsch, Gropp et aI., 1991). Acetosyringenin was shown to be the most effective inhibi- tor of bronchial constriction in an in vivo comparison of 25 acetophenones with the plethysmographic guinea pig mod- el (Dorsch, Muller, Christoffel et aI., 1994).