Pre-mutagenic and mutagenic changes imprinted on the genomes of mammalian cells after irradiation with a nail polish dryer

ABSTRACTUltraviolet A light (UVA) is commonly emitted by nail polish dryers with recent reports suggesting that long-term use of UV-nail polish dryers may increase the risk for developing skin cancer. However, no experimental evaluation has been conducted to reveal the effect of radiation emitted by UV-nail polish dryers on mammalian cells. Here, we examine the pre-mutagenic and mutagenic changes imprinted on the genomes of human and murine primary cell models due to irradiation by a UV-nail dryer. Our findings demonstrate that radiation from UV-nail devices is cytotoxic and genotoxic. Importantly, high levels of reactive oxygen species were observed in all irradiated samples. Analysis of somatic mutations revealed a dose-dependent increase of C:G>A:T substitutions in irradiated samples with a pattern consistent to the one of COSMIC signature 18, a mutational signature attributed to reactive oxygen species. Examination of previously generated skin cancer genomics data revealed that signature 18 is ubiquitously present in melanoma and that it accounts for ~12% of the observed driver mutations. In summary, this study demonstrates that radiation emitted by UV-nail polish dryers can both damage DNA and can permanently imprint somatic mutations on the genomes of mammalian cells. These results have far reaching implications in regard to public health and to preventing skin cancer due to occupational- or consumer-based exposure to ultraviolet light from artificial sources.

Działanie przeciwmutagenne i przeciwgenotoksyczne propolisu

The literature data indicate that propolis is distinguished by anti-mutagenic and anti-genotoxic activity. Mutagenicity is characterized by the formation of permanent and hereditary changes in the structure of the genetic material of a cell or organism. However, genotoxicity is associated with the harmful effects of substances on genetic material. To determine the anti-mutagenic and anti-genotoxic effect, a microbiological test using the histidine-dependent Salmonella typhimurium strains (Ames Test) is applied, and in pharmacological studies mutations in mammalian cells and recess mutations in the fruit fly Drosophila melanogaster are determined. A review of the literature indicates that ethanol and aqueous extracts from propolis have got a significant anti-mutagenic and anti-genotoxic influence on many substances that cause mutagenic changes and that damage genetic material. Research indicates that propolis extracts used in therapeutic doses are safe for the human body. Mutagenic and genotoxic effects may only be induced by doses that are many times higher than therapeutic doses, i.e. above 1 g/kg body weight daily.

Flavinylation in wild-type trimethylamine dehydrogenase and differentially charged mutant enzymes: a study of the protein environment around the N1 of the flavin isoalloxazine

In wild-type trimethylamine dehydrogenase, residue Arg-222 is positioned close to the isoalloxazine N1/C2 positions of the 6S-cysteinyl FMN. The positively charged guanidino group of Arg-222 is thought to stabilize negative charge as it develops at the N1 position of the flavin during flavinylation of the enzyme. Three mutant trimethylamine dehydrogenases were constructed to alter the nature of the charge at residue 222. The amount of active flavinylated enzyme produced in Escherichia coli is reduced when Arg-222 is replaced by lysine (mutant R222K). Removal or reversal of the charge at residue 222 (mutants R222V and R222E, respectively) leads to the production of inactive enzymes that are totally devoid of flavin. A comparison of the CD spectra for the wild-type and mutant enzymes revealed no major structural change following mutagenesis. Like the wild-type protein, each mutant enzyme contained stoichiometric amounts of the 4Fe-4S cluster and ADP. Electrospray MS also indicated that the native and recombinant wild-type enzymes were isolated as a mixture of deflavo and holo enzyme, but that each of the mutant enzymes have masses expected for deflavo trimethylamine dehydrogenase. The MS data indicate that the lack of assembly of the mutant proteins with FMN is not due to detectable levels of post-translational modification of significant mass. The experiments reported here indicate that simple mutagenic changes in the FMN-binding site can reduce the proportion of flavinylated enzyme isolated from Escherichia coli and that positive charge is required at residue 222 if flavinylation is to proceed.

Die Basenspezifität bei der Induktion von Mutationen durdh salpetrige Säure im Phagen T2

In phage T2 treated with nitrous acid (HNO2) the deamination rates of the amino-bases G, A and HMC can be shifted relative to each other by altering the pH of treatment. Under various pH conditions the variation of the rates of HNO2-induced r- mutation and inactivation have been measured and compared to the corresponding alteration of the deamination rates. In this way it was shown, that the deamination of the bases A and HMC can lead to mutagenic changes, whereas the deamination of G can only act lethally. Furthermore it was estimated, that the deamination of any one of 370 base pairs of the rII-region give rise to a mutation. Deamination of ∼1/4 of the bases within the total T2-DNA lead to inactivation.