Development of transient mutagenic activity following the chlorination of the sunscreen UV filter dioxybenzone (benzophenone-8) in bromide-rich water.

The mutagenicity of four organic UV filters namely oxybenzone (benzophenone-3), dioxybenzone (benzophenone-8), avobenzone, and octyl methoxycinnamate, in chlorinated bromide-rich water (artificial seawater) was investigated. Mutagenicity was evaluated using Ames test in Salmonella typhimurium TA98 without S9 mix. Chemical analysis using high-resolution mass spectrometry was carried out to elucidate the mutagenic transformation products. Among the studied UV filters, only dioxybenzone exhibited a clear mutagenic activity following chlorination in seawater at ratio 1:10 (UV filter:chlorine). In contrast, no mutagenic activity was detected when chlorine was added at higher doses (ratio 1:1000). High-resolution mass spectrometry analysis showed that mutagenic extracts contained several brominated transformation products of dioxybenzone. Time course analysis of the transformation products at increasing chlorine doses showed that they were unstable and disappeared more quickly at higher chlorine doses. This instability explained the absence of mutagenic activity of dioxybenzone when 1000-fold excess chlorine was added, as no transformation products were detected. Relevance of these findings to the context of swimming pool is discussed. Further investigations taking into consideration the mutagenicity of not only the intermediate transformation products but also the final disinfection byproducts are needed to determine the overall impact of high levels of chlorine on the overall mutagenicity. This study highlights the importance of considering the reactivity of organic UV filters and their transformation products in disinfected recreational waters when sunscreen formulations are prepared.

Use of low density polyethylene membranes for assessment of genotoxicity of PAHs in the Seine River.

The genotoxicity of river water dissolved contaminants is usually estimated after grab sampling of river water. Water contamination can now be obtained with passive samplers that allow a time-integrated sampling of contaminants. Since it was verified that low density polyethylene membranes (LDPE) accumulate labile hydrophobic compounds, their use was proposed as a passive sampler. This study was designed to test the applicability of passive sampling for combined chemical and genotoxicity measurements. The LDPE extracts were tested with the umu test (TA1535/pSK1002 ± S9) and the Ames assay (TA98, TA100 and YG1041 ± S9). We describe here this new protocol and its application in two field studies on four sites of the Seine River. Field LDPE extracts were negative with the YG1041 and TA100 and weakly positive with the TA98 + S9 and Umu test. Concentrations of labile mutagenic PAHs were higher upstream of Paris than downstream of Paris. Improvement of the method is needed to determine the genotoxicity of low concentrations of labile dissolved organic contaminants.

Assessing the genotoxicity of two commonly occurring byproducts of water disinfection: Chloral hydrate and bromal hydrate.

Water disinfection treatments result in the formation of disinfection byproducts (DBPs) that have been linked to adverse human health outcomes including higher incidence of bladder and colorectal cancer. However, data about the genotoxicity of DBPs is limited to only a small fraction of compounds. Chloral hydrate (CH) and bromal hydrate (BH) are two trihaloacetaldehydes commonly detected in disinfected waters, but little is known about their genotoxicity, especially BH. We investigated the genotoxicity of CH and BH using a test battery that includes three in vitro genotoxicity assays. We conducted the Ames test using Salmonella bacterial strains TA97a, TA98, TA100 and TA102, and the alkaline comet assay and the micronucleus test both using Chinese hamster ovary cells. We carried out the tests in the absence and presence of the metabolic fraction S9 mix. CH did not exhibit statistically significant genotoxic effects in any of the three assays. In contrast, BH exhibited mutagenic activity in the Salmonella strain TA100 and induced statistically significant DNA lesions in CHO cells as appeared in the comet assay. The genotoxic potential of BH in both assays decreased in the presence of the metabolic fraction S9 mix. BH did not induce chromosomal damage in CHO cells. Our results show that BH exhibited genotoxic activity by causing mutations and primary DNA damage while CH did not induce genotoxic effects. Our findings highlight concerns about the higher genotoxicity of brominated DBPs in comparison to their chlorinated analogues.

Identification of disinfection by-products in freshwater and seawater swimming pools and evaluation of genotoxicity.

Exposure to disinfection byproducts (DBPs) in swimming pools has been linked to adverse health effects. Numerous DBPs that occur in swimming pools are genotoxic and carcinogenic. This toxicity is of a greater concern in the case of brominated DBPs that have been shown to have substantially greater toxicities than their chlorinated analogs. In chlorinated seawater swimming pools, brominated DBPs are formed due to the high content of bromide. Nevertheless, very little data is reported about DBP occurrence and mutagenicity of water in these pools. In the present study, three seawater and one freshwater swimming pools located in Southeastern France were investigated to determine qualitatively and quantitatively their DBP contents. An evaluation of the genotoxic properties of water samples of the freshwater pool and a seawater pool was conducted through the Salmonella assay (Ames test). The predominant DBPs identified in the freshwater pool were chlorinated species and included trichloroacetic acid, chloral hydrate, dichloroacetonitrile, 1,1,1-trichloropropanone and chloroform. In the seawater pools, brominated DBPs were the predominant species and included dibromoacetic acid, bromoform and dibromoacetonitile. Bromal hydrate levels were also reported. In both types of pools, haloacetic acids were the most prevalent chemical class among the analyzed DBP classes. The distribution of other DBP classes varied depending on the type of pool. As to genotoxicity, the results of Ames test showed higher mutagenicity in the freshwater pool as a consequence of its considerably higher DBP contents in comparison to the tested seawater pool.

Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study.

UNLABELLED: The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. METHODS: Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045-45 y/o, smokers, and small drinkers (24-hour urinary volume <1 L and osmolality >700 mOsmol/kg). OUTCOMES: 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. TEST GROUP: Subjects consumed 1.5 L daily of the study product (EVIAN) on top of their usual water intake for 50 days. CONTROL GROUP: Subjects continued their usual lifestyle habits. RESULTS: 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary.

Genotoxic and oxidative responses in coelomocytes of Eisenia fetida and Hediste diversicolor exposed to lipid-coated CdSe/ZnS quantum dots and CdCl2.

The emerging of Quantum Dots utilization in industrial or medicinal fields involved a potentially increase of these nanoparticles in environment. In this work, the genotoxic (comet assay) and oxidative effects (SOD activity, TBARS) of functionalized-QDs and cadmium chloride were investigated on Hediste diversicolor and Eisenia fetida coelomocytes. Results demonstrated that functionalized-QDs (QDNs) and cadmium chloride induced DNA damages through different mechanisms that depended on the nano- or ionic nature of Cd. The minimal genotoxic concentrations for H. diversicolor (<0.001ng/g for QDNs and CdCl2 ) were lower than for E. fetida (between 0.01 and 0.1 ng/g for QDNs, and between 0.001 and 0.01 ng/g for CdCl2 ). These results showed that H. diversicolor was more sensitive than E. fetida. The two contaminants had a low impact on the oxidative stress markers.

New Ianthelliformisamine derivatives as antibiotic enhancers against resistant Gram-negative bacteria.

A series consisting of ianthelliformisamimes A, B, and C as well as its synthetic analogues was prepared in high chemical yield, from 27 to 91%, using peptide coupling as the key step, and the compounds were evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives against Pseudomonas aeruginosa when combined with doxycycline was precisely evaluated utilizing bioluminescence to measure ATP efflux and fluorescence to evaluate membrane depolarization.

In vitro cytotoxic and anticlastogenic activities of saxifragifolin B and cyclamin isolated from Cyclamen persicum and Cyclamen libanoticum.

CONTEXT: The genus Cyclamen L. (Primulaceae) is rich in saponins known to have interesting biological activities. OBJECTIVE: To isolate saxifragifolin B and cyclamin, two triterpene saponins, from Cyclamen libanoticum Hildebr and Cyclamen persicum Mill, and to assess their cytotoxic, clastogenic/aneugenic, and anticlastogenic effects, as well as antioxidant potential. MATERIALS AND METHODS: Saxifragifolin B and cyclamin were tested for their cytotoxicity against SK-BR-3, HT-29, HepG2/3A, NCI-H1299, BXPC-3, 22RV1, and normal DMEM cell lines using WST-1 assay. Their clastogenic/aneugenic activities and anticlastogenic effects against the anticancer drug mitomycin C were assessed by the in vitro micronucleus assay in CHO cells. Their antioxidant capacities were determined using Fe(2+)-chelating and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays. RESULTS: Both saponins were described for the first time in Cyclamen libanoticum. They showed strong cytotoxic activities against the tested cancer cell lines. Saxifragifolin B was found to be 56- and 37-times more active than mitomycin C against breast adenocarcinoma (SK-BR-3) and lung carcinoma (NCI-H1299), respectively. Also, saxifragifolin B did not induce micronuclei formation and prevented cells from mitomycin C clastogenic effect. Cyclamin induced a significant increase of micronucleated cells after metabolic activation with S9 mix, and did not possess any anticlastogenic activity. Both molecules exhibited low antioxidant activities as compared to reference compounds. DISCUSSION AND CONCLUSIONS: This study showed the remarkable cytotoxic activity of saxifragifolin B, especially against breast adenocarcinoma and lung carcinoma and its chemoprotective activity against mitomycin C. Thus, saxifragifolin B could be suggested as a potential cytotoxic drug with a preventive effect against possible exposures to genotoxic agents.

Genotoxicity of intraperitoneal injection of lipoamphiphile CdSe/ZnS quantum dots in rats.

The main objective of the present in vivo rat study was to determine the genotoxicity of lipoamphiphile-coated CdSe/ZnS Quantum Dots (QDs), in several organs (brain, liver, kidneys, lungs and testicles). The second objective was to establish the correlations between the QDs genotoxic activity and the oxidative stress, the production of a proinflammatory cytokine (TNF-α), a stress-induced chaperone protein, the phosphorylated heat shock protein 70 (pHsp70), and an increase in the caspase-3 apoptosis factor. Four QDs doses were injected into the peritoneal cavity (5, 5×10(-1), 5×10(-2) and 5×10(-3)µg/kg). DNA lesions in the different organs were measured by the comet assay, and chromosome abnormalities were evaluated by the micronucleus assay on blood reticulocytes (MNRET). Twenty-four hours after the QDs injection, genotoxic effects were observed in the brain and liver and, only for the highest QDs concentration, in testicles. No genotoxic effect was seen in the kidney and lung. The MNRET test revealed a dose-response induction of micronuclei. In parallel, we did neither reveal oxidative stress nor significant variations of TNF-α, pHsp70, and caspase-3. In conclusion, the QDs exerted significant genotoxic effects in the brain and liver, even in the absence of any associated oxidative stress and inflammatory processes.

Genotoxicity assessment of mouse oocytes by comet assay before vitrification and after warming with three vitrification protocols.

OBJECTIVE: To assess the genotoxicity of three oocyte vitrification protocols. DESIGN: Murine assay. SETTING: Biogenotoxicology research laboratory. ANIMAL(S): CD1 female mice. INTERVENTION(S): Three mouse oocyte groups were exposed to three commercialized human oocyte vitrification protocols. Protocols 1 and 2 contained dimethyl sulfoxide and ethylene glycol (EG), and protocol 3 contained EG and 1,2-propanediol (PrOH). DNA damage was first evaluated by comet assay after oocyte exposure to the three different equilibration and vitrification solutions. Comet assay was also performed after full vitrification and warming procedure and compared with a negative control group (oocytes stored in medium culture only) and a positive control group (oocytes exposed to hydrogen peroxide just before comet assay). MAIN OUTCOME MEASURE(S): DNA damage was quantified as Olive tail moment (OTM). Statistical analysis consisted of a Shapiro-Wilk test. Then, median protocol OTM was compared with the negative control group with the Mann-Whitney U test. The difference was considered to be statistically significant if the P value was <.05. RESULT(S): In both parts of our study, protocols 1 and 2 did not induce significant DNA damage, whereas protocol 3 induced statistically higher DNA damage compared with the negative control group. CONCLUSION(S): Vitrification protocols containing PrOH induced significant DNA damage on mouse oocytes, both before cooling and after warming. Therefore, for the moment, we prefer vitrification techniques without PrOH while we await more studies on PrOH toxicity and long-term evaluation.

Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots.

We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core-shell QDs encapsulated by a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and functionalized by a nucleolipid N-[5'-(2',3'-di-oleoyl) uridine]-N',N',N'-trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic, mutagenic and clastogenic effects of QDsN were compared to those of cadmium chloride (CdCl(2)). Three assays were used: (1) the Salmonella/microsome assay with four tester strains, (2) the comet assay and (3) the micronucleus test on CHO cells. The contribution of simulated sunlight was studied in the three assays while oxidative events were only explored in the comet assay in aliquots pretreated with the antioxidant l-ergothioneine. We found that QDsN could enter CHO-K1 cells and accumulate in cytoplasmic vesicles. It was not mutagenic in the Salmonella/mutagenicity test whereas CdCl(2) was weakly positive. In the dark, both the QDsN and CdCl(2) similarly induced dose-dependent increases in single-strand breaks and micronuclei. Exposure to simulated sunlight significantly potentiated the genotoxic activities of both QDsN and CdCl(2), but did not significantly increase micronucleus frequencies. l-Ergothioneine significantly reduced but did not completely suppress the DNA-damaging activity of QDsN and CdCl(2). The present results clearly point to the genotoxic properties and the risk of long-term adverse effects of such a nanoplatform if used for human anticancer therapy and diagnosis in the future.

Influence of the length of imogolite-like nanotubes on their cytotoxicity and genotoxicity toward human dermal cells.

Physical-chemical parameters such as purity, structure, chemistry, length, and aspect ratio of nanoparticles (NPs) are linked to their toxicity. Here, synthetic imogolite-like nanotubes with a set chemical composition but various sizes and shapes were used as models to investigate the influence of these physical parameters on the cyto- and genotoxicity and cellular uptake of NPs. The NPs were characterized using X-ray diffraction (XRD), small angle X-ray scattering (SAXS), and atomic force microscopy (AFM). Imogolite precursors (PR, ca. 5 nm curved platelets), as well as short tubes (ST, ca. 6 nm) and long tubes (LT, ca. 50 nm), remained stable in the cell culture medium. Internalization into human fibroblasts was observed only for the small particles PR and ST. None of the tested particles induced a significant cytotoxicity up to a concentration of 10(-1) mg·mL(-1). However, small sized NPs (PR and ST) were found to be genotoxic at very low concentration 10(-6) mg·mL(-1), while LT particles exhibited a weak genotoxicity. Our results indicate that small size NPs (PR, ST) were able to induce primary lesions of DNA at very low concentrations and that this DNA damage was exclusively induced by oxidative stress. The higher aspect ratio LT particles exhibited a weaker genotoxicity, where oxidative stress is a minor factor, and the likely involvement of other mechanisms. Moreover, a relationship among cell uptake, particle aspect ratio, and DNA damage of NPs was observed.

Genotoxicity of sediment extracts of the Berre lagoon (France).

To evaluate the genotoxic risk that contaminated sediment could constitute for benthic organisms, three contaminated (VA, VC and VN) and one uncontaminated (RN) sediment samples were collected in the Berre lagoon (France). Potentially bioavailable contaminants in sediments were obtained using sediment extraction with synthetic seawater adjusted to pH 4 or pH 6, simulating the range of pH prevailing in the digestive tract of benthic organisms. The genotoxic activities of these extracts were evaluated by three short-term bioassays: the Salmonella mutagenicity test using the Salmonella typhimurium strain TA102, the alkaline comet assay and the micronucleus assay on the Chinese Hamster Ovary cells CHO-K1. Results of the Salmonella mutagenicity assay detected a mutagenic response for RN extract at pH 6, and for VA extract at pH 4. Results of the comet and micronucleus assays detected low genotoxic/clastogenic activities for VA and VC extracts at pH 6 and higher activities for RN, VA and VC extracts at pH 4. To identify if metals (Al, Fe, Mn, As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn) were involved in these genotoxic activities, their concentrations were determined in the extracts, and their speciation was assessed by thermodynamic calculations. Results showed that extracts from sites VA, VC and VN generally presented the highest trace metal contents for both extractants, while the site RN presented lower trace metal contents but the highest Fe and Mn contents. Thermodynamic calculations indicated that Fe, Mn, As and in a lower extend Co, Ni and Zn were mainly present under free forms in extracts, and were consequently, more likely able to induce a genotoxic effect. Results globally showed no correspondence between free metal contents and genotoxic activities. They suggested that these positive results could be due to uncharacterized compounds, acting as direct genotoxic agents or enhancing the genotoxic properties of analyzed metals.

Assessment of 1,2-propanediol (PrOH) genotoxicity on mouse oocytes by comet assay.

OBJECTIVE: To assess the genotoxicity of 1,2-propanediol (PrOH) on mouse oocytes by comet assay. DESIGN: In vitro assay using murine model. SETTING: Biogenotoxicology research laboratory. ANIMAL(S): CD1 female mice. INTERVENTION(S): Three 40-oocyte groups were exposed to different PrOH concentrations (5%, 7.5%, and 15%). Each concentration was tested during both long and short exposures (1-2 hours and 1-5 minutes) in comparison with control groups. DNA damage was evaluated by a single-cell gel electrophoresis assay, also called "comet assay," and analyzed with Komet software. MAIN OUTCOME MEASURE(S): DNA damage was quantified as Olive tail moment (OTM). Interpretation was done on OTM with the use of χ(2). RESULT(S): High PrOH concentrations (7.5% and 15%) induced significant DNA damage on mouse oocytes. The OTM χ(2) values were 4.16 ± 0.40 and 6.80 ± 0.4 with 7.5% PrOH at 1 and 2 hours, respectively, 24.35 ± 1.60 with 15% at 1 hour, and for 2h at 15% the DNA damage was too drastic to calculate OTM χ(2). After 1 and 5 minutes, the OTM χ(2) values were, respectively, 5.19 ± 0.26 and 6.06 ± 0.42 with 7.5%, and 7.53 ± 0.33 and 16.81 ± 0.67 with 15%. CONCLUSION(S): High concentrations of PrOH (7.5% and 15%) induced significant DNA damage on mouse oocytes, whatever the exposure duration. These results should be interpreted with caution, because additional data are needed to evaluate PrOH genotoxicity and DNA oocyte reparation after exposure to high PrOH concentrations.

Comparison of two extraction procedures for the assessment of sediment genotoxicity: implication of polar organic compounds.

Four sediment samples (Vaïne Airport VA, Vaïne Center VC, Vaïne North VN and Reference North RN) were collected in the Berre lagoon (France). Sediments were analyzed for polycyclic aromatic hydrocarbons (PAHs) by use of pressurized fluid extraction with a mixture of hexane/dichloromethane followed by HPLC with fluorescence detection analysis. Organic pollutants were also extracted with two solvents for subsequent evaluation of their genotoxicity: a hexane/dichloromethane mixture intended to select non-polar compounds such as PAHs, and 2-propanol intended to select polar contaminants. Sediment extracts were assessed by the Salmonella/microsome mutagenicity test with Salmonella typhimurium TA98+S9 mix and YG1041±S9 mix. Extracts were also assessed for their DNA-damaging activity and their clastogenic/aneugenic properties by the comet assay and the micronucleus test with Chinese Hamster ovary (CHO) cells. The PAH concentrations were 611ngg(-1)dw, 1341ngg(-1) dw, 613ngg(-1)dw and 482ngg(-1)dw for VA, VC, VN and RN, respectively. Two genotoxic profiles were observed, depending on the extraction procedure. All the non-polar extracts were mutagenic for TA98+S9 mix, and VA, VC, VN sediment samples exerted a significant DNA-damaging and clastogenic activity in the presence of S9 mix. All the polar extracts appeared mutagenic for TA98+S9 mix and YG104±S9 mix, and VA, VC, VN were genotoxic and clastogenic both with and without S9 mix. These results indicate that the genotoxic and mutagenic activities mainly originated from PAHs in the non-polar extracts, while these activities came from other genotoxic contaminants, such as aromatic amines and nitroarenes, in the polar extracts. This study focused on the important role of uncharacterized polar contaminants such as nitro-PAHs or aromatic amines in the global mutagenicity of sediments. The necessity to use appropriate extraction solvents to accurately evaluate the genotoxic hazard of aquatic sediments is also highlighted.

Evaluation of the mutagenic/clastogenic potential of 3,6-di-substituted acridines targeted for anticancer chemotherapy.

The mutagenicity and clastogenicity of a series of 18 3,6-di-substituted acridines were evaluated by the Ames test on Salmonella typhimurium TA 97a and by the micronucleus assay on Chinese Hamster Ovary cells (CHO cells), as compared to their cytotoxicity against CHO cells. Experimental results overall demonstrated that simple symmetric molecules were more mutagenic than asymmetric structures. The mutagenic properties of acridines on strain TA97a mainly depended on molecular geometry and length, and on the nature of the substituted groups. The clastogenicity of acridines mainly depended on molecular length and electrophilicity in mammalian cells. Structure-activity relationships indicated that cytotoxicity could be decoupled from genotoxicity by introducing several chemical groups that induced asymmetry or bulkiness in the acridine compounds. They led to the synthesis of the promising 3-acetamido-6-(4-fluorobenzamido)acridine, which displayed a strong cytotoxic activity and was not mutagenic.

Comet assay on mouse oocytes: an improved technique to evaluate genotoxic risk on female germ cells.

OBJECTIVE: To develop and validate an efficient comet assay on mouse oocytes without depellucidation. DESIGN: In vitro experiments using a murine model. SETTING: Biogenotoxicology research laboratory in Aix-Marseille II University, France. ANIMAL(S): CD1 prepubescent female mice. INTERVENTION(S): DNA lesions in oocytes were evaluated by the alkaline comet assay. After oocyte retrieval, we first studied the effect of zona pellucida (ZP) on comet morphology. For this study, we applied the comet assay to mature oocytes with and without ZP after exposure to simulated sunlight irradiation (SSI) compared with negative controls. Next, nondepellucidated mouse oocytes were exposed to three well-known genotoxic agents (SSI, methylmethanesulfonate [MMS], and hydrogen peroxide [H(2)O(2)]) and compared with negative controls. Images of oocytes were analyzed with Komet software. MAIN OUTCOME MEASURE(S): DNA damages were quantified and expressed as olive tail moment (OTM), defined as the product of the tail length and the fraction of total DNA in the tail. OTMχ(2) were calculated from OTM; they corresponded to the degrees of freedom (n) of each OTM distribution obtained from at least 50 oocytes. OTMχ(2) is an indicator of DNA lesions. The test was considered positive and statistically significant when OTMχ(2) increased in oocytes compared with the medium-only control cells. RESULT(S): There was no difference in comet aspect between oocyte groups with and without ZP. The three genotoxic agents significantly increased DNA damages as compared with the control groups. The OTMχ(2) values were (mean ± SD): 2.1 ± 0.07, 7.73 ± 0.35, 3.35 ± 0.15, and 12.4 ± 0.51 in control, SSI, MMS, and H(2)O(2) groups, respectively. CONCLUSION(S): Comet assay on non depellucidated mouse oocytes is a rapid and easy test. This assay would be useful to assess the genotoxicity on female germ cells of chemicals, drugs, or environmental pollutants and the efficiency of antioxidant molecules.

Organic pollution and genotoxicity of sediments of the Palun marshes (Berre lagoon, France).

The impact of industrial, rural, and urban activities on two runnels (B1, B2, and B3 from Beausset runnel and V1 and V2 from Vallat du Ceinturon runnel) located in the Palun marshes (Berre lagoon, France) was evaluated by analyzing 16 polycyclic aromatic hydrocarbons (PAHs), 1-nitropyrene (1-NP), 1-aminopyrene (1-AP), and six pesticides in sediment samples. The mutagenicity was assessed with the Salmonella mutagenicity test using tester strains TA98+S9 Mix and YG1041 +/- S9 Mix. The clastogenicity was evaluated with the micronucleus assay on Chinese Ovarian cells +/- S9 Mix. A gradient of PAHs concentrations was observed from B1 (3359 microg kg(-1) dry weight [dw]), close to industrial zones, to V2 (497 microg kg(-1) dw), away from the source of pollution. Similar gradient was noted for 1-AP (from B1: 11.8 microg kg(-1) dw to V2: 0.6 microg kg(-1) dw). However, this trend was not observed in 1-NP concentrations (concentrations ranged from 1.2 microg kg(-1) dw [V1] to 0.4 microg kg(-1) dw [B1]). Pesticides were detected in all samples. Diazinon and dieldrin were found in high concentrations in B1 extracts (74.5 and 39.9 microg.kg(-1) dw, respectively). All the sediments except V2 were mutagenic with strain TA98+S9 Mix. The mutagenicity was linked to the presence of PAHs (V1), nitroarenes (B1 and B3) and aromatic amines (B2). All sediments were clastogenic with and without S9 Mix except V1 extract, which was negative without S9 Mix. Overall, the two runnels in the Palun marshes were found to be polluted by many organic compounds that originate from direct human activities and pose a significant genotoxic risk.

DNA-damaging, mutagenic, and clastogenic activities of gentiopicroside isolated from Cephalaria kotschyi roots.

Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria kotschyi roots. The mutagenicity, DNA-damaging capacities, and clastogenicity of this molecule were evaluated by the Salmonella typhimurium mutagenicity assay (Ames test) on tester strains TA97a, TA98, TA100, and TA102, the alkaline comet assay, and the micronucleus assay on CHO cells. All tests were performed with and without the metabolization mixture, S9 mix. In the Ames test, the mutagenicity of 1 was limited to TA102 without S9 mix (2.3 rev microg(-1)). The genotoxicity was more evident without S9 mix (0.78 OTMchi(2) units microg(-1) mL) than with the metabolic mixture (0.16 OTMchi(2) units microg(-1) mL) with the comet assay. Similarly, the clastogenicity without S9 mix was 0.99 MNC microg(-1) mL and 0.38 MNC microg(-1) mL with S9 mix in the micronucleus assay. The interaction of 1 with DNA is probably through the involvement of oxidative DNA lesions.

Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine.

The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.