The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

<p>Abstract</p> <p>Background</p> <p>In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in <it>XPC, ERCC2 and ERCC5 </it>genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade.</p> <p>Methods</p> <p>The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique.</p> <p>Results</p> <p>Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99). Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade.</p> <p>Conclusion</p> <p>These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.</p

Multiple Analytical Approaches Reveal Distinct Gene-Environment Interactions in Smokers and Non Smokers in Lung Cancer

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p<0.001 and OR = 0.51;95%CI = 0.33–0.78,p = 0.002 respectively). In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His), SULT1A1 213GG (Arg/Arg) or AA (His/His) and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33–10.55,p = 0.006), whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg) and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15–7.51,p = 0.01). MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His) and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His) with testing balance accuracy (TBA) of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with SULT1A1 Arg213His and EPHX1 Tyr113His in smokers and SULT1A1 Arg213His with GSTP1 Ile105Val and CYP1A1*2C in nonsmokers. These results identified distinct gene-gene and gene environment interactions in smokers and non-smokers, which confirms the importance of multifactorial interaction in risk assessment of lung cancer

Activity of secondary metabolites from Penicillium expansum R82 strain against postharvest fungal pathogens

In search for alternative means to conventional fungicides for postharvest disease control, a Penicillium expansum strain (R82) was assayed for its inhibitory activity against mycelial growth and conidial germination of some fungal pathogens. For this purpose a sterile fungal filtrate (SFF) was prepared from malt extract broth previously inoculated with R82 and incubated at 20°C for 10 days. The SFF was tested in vitro for inhibition of mycelium dry weight (DMW) or conidial germination of Botrytis cinerea, Colletotricum acutatum, Monilinia laxa and six P. expansum strains. All pathogens showed a significant decrease of DWM when grown in SFF of R82 with respect to the control. The highest growth inhibition was observed in P. expansum strains (-75.5%) followed by M. laxa (-63%), C. acutatum (-58%) and B. cinerea (-56%). The conidial germination of the six P. expansum strains was not inhibited by SFF and in some cases was stimulated. In all tested strains, microscopic observations of germinated conidia showed a consistent increase of the length of the germ tube compared to the control, however, the treated germ tubes appeared to be abnormal. Since the thin-layer chromatography tests revealed that the extracts from R82 SFF have no inhibitory activity against the target pathogens, a possible action of volatile organic compounds (VOCs) was supposed. The VOCs produced by R82 strain fully inhibited mycelial growth of B. cinerea, C. acutatum and M. laxa, while a growth reduction occurred in P. expansum strains. Conidial germination of B. cinerea, C. acutatum and M. laxa were completely inhibited, while in P. expansum ranged 18.1 to 32%, compared to the control. The potential of VOCs produced by P. expansum R82 strain as biofumigant is discussed

Biocontrol of apple postharvest decay by Aureobasidium pullulans

The activity of two biological control agents, strains L1 and L8, previously identified as Aureobasidium pullulans, was tested for the first time in the same experiments on apple, artificially inoculated with Botrytis cinerea (grey mould), Colletotrichum acutatum (bitter rot) or Penicillium expansum (blue mould). The washed cells of antagonists controlled over 86% of three decays and the antagonist L1 seemed more efficient than L8. The cell concentration of both antagonists was highly correlated with their efficacy, the R2 ranging from 0.93 to 0.99. The highest concentration (108 CFU ml-1) of L1 and L8 provided the best control of B. cinerea, C. acutatum and P. expansum, although gray mould was completely inhibited also by a concentration one log lower (107 CFU ml-1). The population dynamic of L1 and L8 strains in ‘Gala’ apple increased almost eightfold during the first 48 h after treatment and remained elevated until 7 days, revealing that, although antagonists were isolated from carposhere of peach fruit, they showed good adaptation in other wound environments such as apple, making them suitable for pathogen control in a wide range of hosts. Preliminary in vitro trials were conducted in order to investigate the mechanisms of action of L1 and L8 strains. Both the washed cells showed a complete control of all three pathogens, while the culture filtrates and autoclaved cells were found to have had no significant inhibition on pathogens. In a dual culture dish assay, where there was neither physical contact between antagonists and pathogens nor fungal diffusion through the culture medium, the antifungal effects observed on pathogen mycelium growth could be attributed to the production of volatile organic compounds (VOCs) generated by the antagonists. The VOCs significantly inhibited the growth of all three tested pathogens compared to the control, albeit with a different rate. L1 strain also showed a curative effect; indeed when an antagonist-based-treatment was carried out twelve hours from inoculum, the incidence of blue mould and bitter rot was reduced by 38% and 50% respectively, while the greatest inhibition of grey mould was observed when fruit were treated with the antagonist six hours from the inoculum. In conclusion, A. pullulans L1 and L8 strains could be considered good candidates for the development of biofungicides for postharvest application in the pomefruit industry

Control of postharvest fungal pathogens by antifungal compounds from Penicillium expansum

The fungicidal effects of secondary metabolites produced by a strain of Penicillium expansum (R82) in culture filtrate and in a double petri dish assay were tested against one isolate each of Botrytis cinerea, Colletotrichum acutatum, and Monilinia laxa and six isolates of P. expansum, revealing inhibitory activity against every pathogen tested. The characterization of volatile organic compounds released by the R82 strain was performed by solid-phase microextraction\u2013gas chromatographic techniques, and several compounds were detected, one of them identified as phenethyl alcohol (PEA). Synthetic PEA, tested in vitro on fungal pathogens, showed strong inhibition at a concentration of 1,230 mg/ml of airspace, and mycelium appeared more sensitive than conidia; nevertheless, at the concentration naturally emitted by the fungus (0.726 \ua1 0.16 mg/ml), commercial PEA did not show any antifungal activity. Therefore, a combined effect between different volatile organic compounds produced collectively by R82 can be hypothesized. This aspect suggests further investigation into the possibility of exploiting R82 as a nonchemical alternative in the control of some plant pathogenic fungi

Antifungal Activity of Essential Oils of Origanum majorana and Lavender angustifolia against Fusarium Wilt and Root Rot Disease of Melon Plan

The objective of this study was to evaluate the antifungal activity of essential oils of marjoram (Origanum majorana) and lavender (Lavender angustifolia) against eleven isolates of Fusarium oxysporum f. sp. melonis and ten isolates of Fusarium solani, the causal agents of Fusarium wilt and root rot disease of melon. The effect of essential oils on disease development under in vivo conditions was also tested. GC-MS analysis of marjoram essential oils showed that terpinen-4-ol (34.94%) is the major component, followed by γ-terpinene (24.66%), α-terpinene (13.22%), β-terpinene (5.84%), αterpineol (3.98%), and β-phellandrene (3.16%). Chemical analysis of lavender essential oils showed that α-terpinene (48.76%) is the major component, followed by linalool (16.79%), γ-terpinene (7.00%), β-trans-ocimane (6.47%), β-caryophyllene (5.83%), and lavandulol (3.23%). All essential oils tested in vitro using the disk diffusion method revealed a significant antifungal effect against mycelium growth of all F. oxysporum f. sp. melonis and F. solani isolates. The volatile compounds of essential oils have completely inhibited spore germination of both pathogens. In vivo, the essential oils applied as biofumigant significantly reduced disease severity on melon plants 20 days post-incubation. Lavender essential oils significantly reduced disease severity by almost 60% as compared to control melon plants while Marjoram essential oils reduced disease severity by almost 23% under controlled conditions. These results showed that lavender essential oils may contribute to the development of new antifungal compounds to protect melon crops from Fusarium wilt and root rot diseas

First report of Penicillium ulaiense causing whisker mould on stored citrus fruit in Tunisia

In a survey carried out in January-July 2014, fruits showing blue and/or green efflorescence, were picked in farms and packinghouses of the northeastern part of Cap Bon peninsula, and brought to the laboratory. On infected fruits P. digitatum and P. italicum coexisted with a morphologically distinct Penicillium spp. This latter was sub-cultured on malt extract agar (MEA) and identified, according to its morphological and cultural characteristics, as P. ulaiense, the causal agent of whisker mould, whose distinctive feature is the ability to form coremia (1-7 mm tall) with white stalks arranged in concentric circles or circular patches (Holmes et al., 1994)