title: Comprehensive assessment of the photomutagenicity, photogenotoxicity and photo(cyto)toxicity of azulene.
abstract: The polycyclic aromatic hydrocarbon azulene and its naturally occurring derivative guaiazulene (1,4-dimethyl-7-isopropylazulene) are known to absorb light in the UV-vis region of the spectrum. Both compounds were reported to be mutagenic in the Salmonella typhimurium bacterial mutagenicity assay (Ames test) in strain TA102, and to cause DNA damage in the comet assay in vitro upon exposure to UVA light. In contrast, another study reported a photoprotective effect in vitro of guaiazulene. We present here a comprehensive assessment of the photo(cyto)toxicity (3T3 fibroblast Neutral Red uptake test), the photomutagenicity (Ames test) and photogenotoxicity (comet assay and micronucleus test in L5178Y cells in vitro) of azulene. In the Ames test, the mutagenicity of azulene was assessed in the presence and absence of UV light by use of the Salmonella strains TA102, TA104, TA2638 and E. coli WP2. Azulene was irradiated before being plated with bacteria (pre-irradiation), or concomitantly with the bacteria either after plating or while in suspension. Guaiazulene was included in some of the experiments. Neither in the photo-Ames test nor in the other photogenotoxicity tests, azulene or guaiazulene showed any photomutagenic or photogenotoxic activity. Weak photo(cyto)toxicity (estimate of PIF≥1.67) was observed with azulene in the 3T3 NRU test, the Alamar Blue test and the relative cell count, which may be due to the generation of reactive oxygen species, as reported recently.
authors.affiliation: F. Hoffmann-La Roche Ltd., Non Clinical Safety, B. 073/215A, Ch-4070 Basel, Switzerland. melanie.struwe@roche.com
authors.forename: M
authors.initials: M
authors.lastname: Struwe
authors.forename: M
authors.initials: M
authors.lastname: Csato
authors.forename: T
authors.initials: T
authors.lastname: Singer
authors.forename: E
authors.initials: E
authors.lastname: Gocke
mesh_terms: D016475:3T3 Cells; D000818:Animals; D052176:Azulenes / Q000633:toxicity*; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage; D007940:Leukemia L5178; D008027:Light / Q000009:adverse effects; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D055668:Photochemical Processes; D012486:Salmonella typhimurium / Q000187:drug effects; D012717:Sesquiterpenes / Q000633:toxicity; D045789:Sesquiterpenes, Guaiane; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D052176:Azulenes; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C004451:guaiazulene; C005525:azulene