Photobiological activity and frameshift mutagenesis of umbelliferone, 7-hydroxycoumarin, with bacterial and mammalian cells
Date
1994
Authors
Lew, Lorelei Linda
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Abstract
Umbelliferone, 7-hydroxycoumarin, is a compound in the well known family of coumarins. It is widely distributed in nature and has had conflicting reports of photobiological activity, but has never been fully investigated. This study examined umbelliferone for photoactivity against various bacterial and mammalian test systems. Umbelliferone was found to be a photosensitizing agent at approximately 0.1 µg against an overlay of E. coli B/s₋₁, a DNA repair deficient bacterium, but not active against wild type E. coli. B/r WP2 try- until the compound was increased to 20 µg. A dose response curve with wild type E. coli was attempted but cell survival did not decrease significantly in a solution irradiation system. Survival did decrease to an average of 36% in an agar irradiation system over 2 experiments. No significant photosensitization could be found against Chinese hamster ovary cells even in 160 µg/ml of compound and after 20.1 kJ/m² of near ultraviolet light (NUV). Umbelliferone was an active frameshift mutagen at 60 µg/ml (P< 0.05) when tested against E. coli lac⁻, z, thiamine and exhibited a dose response relationship when increased sequentially to 175 µg/ml (p<0.0006) but was not active against Salmonella typhimurium TA98 in the Ames test. To investigate the biological target of umbelliferone, the plasmid pTZ18R, encoding an ampicillin resistance gene, was irradiated with NUV in solution with umbelliferone and DMSO as a control. Umbelliferone at 15 µg/ml decreased the number of ampicillin resistant bacterial transformants by 95% versus the control after an NUV dose of 96.48 kJ/m². In conclusion, umbelliferone is a weak photosensitizing and frameshifting agent in certain strains of E. coli. As the two bacterial strains E. coli B/s₋₁ and B/r exhibited a 200 fold difference in sensitivity to umbelliferone and as the ability of umbelliferone to react with pTZ1 BR DNA was clearly demonstrated, umbelliferone appears to be a weak DNA photoalkylating agent.