A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.
Adenoma ; Animals ; Bacteria ; Bacteroides fragilis ; Carcinogenesis* ; Colon ; Colorectal Neoplasms ; Enterotoxins ; Escherichia coli ; Fecal Microbiota Transplantation ; Fusobacterium nucleatum ; Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Mice ; Microbiota* ; Models, Theoretical* ; Mutagens ; Rats ; Virulence ; Virulence Factors

In the screening of marine mangrove derived fungi for lovastatin productivity, endophytic Aspergillus luchuensis MERV10 exhibited the highest lovastatin productivity (9.5 mg/gds) in solid state fermentation (SSF) using rice bran. Aspergillus luchuensis MERV10 was used as the parental strain in which to induce genetic variabilities after application of different mixtures as well as doses of mutagens followed by three successive rounds of genome shuffling. Four potent mutants, UN6, UN28, NE11, and NE23, with lovastatin productivity equal to 2.0-, 2.11-, 1.95-, and 2.11-fold higher than the parental strain, respectively, were applied for three rounds of genome shuffling as the initial mutants. Four hereditarily stable recombinants (F3/3, F3/7, F3/9, and F3/13) were obtained with lovastatin productivity equal to 50.8, 57.0, 49.7, and 51.0 mg/gds, respectively. Recombinant strain F3/7 yielded 57.0 mg/gds of lovastatin, which is 6-fold and 2.85-fold higher, respectively, than the initial parental strain and the highest mutants UN28 and NE23. It was therefore selected for the optimization of lovastatin production through improvement of SSF parameters. Lovastatin productivity was increased 32-fold through strain improvement methods, including mutations and three successive rounds of genome shuffling followed by optimizing SSF factors.
Aspergillus* ; Efficiency ; Fermentation* ; Fungi ; Genome* ; Humans ; Lovastatin* ; Mass Screening ; Mutagens ; Parents

The diethyl sulfate (DES) mutagenesis was chosen for the mutagenic treatment to Phellinus igniarius, and the relationship of mutagenesis time and death rate was investigated with 0.5% DES. The differences of mycelial growth speed, liquid fermentation mycelia biomass, morphology and pigment classes of secondary metabolites production speed and antioxidant activities of metabolite products were discussed. The study displayed that DES mutagenesis could change mycelial morphology without obvious effect on mycelium growth, and the DES mutagenesis improved antioxidant activities of the active ingredients of P. igniarius and had more antioxidant activity of hypoxia/sugar PC12 nerve cells than that of P. igniarius.
Basidiomycota ; drug effects ; genetics ; growth & development ; metabolism ; Mutagenesis ; Mutagens ; pharmacology ; Mycelium ; drug effects ; genetics ; growth & development ; metabolism ; Pigments, Biological ; analysis ; metabolism ; Secondary Metabolism ; drug effects ; Sulfuric Acid Esters ; pharmacology

OBJECTIVEIn this study, a pilot-scale investigation was conducted to examine and compare the biotoxicity of the organic compounds in effluents from five treatment processes (P1-P5) where each process was combination of preoxidation (O3), coagulation, sedimentation, sand filtration, ozonation, granular activated carbon, biological activated carbon and chlorination (NaClO).

METHODSOrganic compounds were extracted by XAD-2 resins and eluted with acetone and dichlormethane (DCM). The eluents were evaporated and redissolved with DMSO or DCM. The mutagenicity and estrogenicity of the extracts were assayed with the Ames test and yeast estrogen screen (YES assay), respectively. The organic compounds were detected by GC-MS.

RESULTSThe results indicated that the mutation ratio (MR) of organic compounds in source water was higher than that for treated water. GC-MS showed that more than 48 organic compounds were identified in all samples and that treated water had significantly fewer types and concentrations of organic compounds than source water.

CONCLUSIONTo different extents, all water treatment processes could reduce both the mutagenicity and estrogenicity, relative to source water. P2, P3, and P5 reduced mutagenicity more effectively, while P1 reduced estrogenicity, most effectively. Water treatment processes in this pilot plant had weak abilities to remove Di-n-butyl phthalate or 1, 2-Benzene dicarboxylic acid.

Estrogens ; toxicity ; Gas Chromatography-Mass Spectrometry ; Mutagens ; toxicity ; Organic Chemicals ; toxicity ; Pilot Projects ; Water Pollutants, Chemical ; toxicity ; Water Purification ; methods

OBJECTIVETo study the effect of Morinda officinalis (MO) extract on cytoxan (CTX) -impaired spermatogenesis of adult male SD rats.

METHODSWe randomly divided 56 adult male SD rats into seven groups of equal number: blank control, CTX model, CTX + NS, CTX + 10 g/kg MO, CTX + 20 g/kg MO, CTX + 30 g/kg MO, and CTX + 40 g/kg MO. We made the models of impaired spermatogenesis in the SD rats by intraperitoneal injection of CTX and treated the animal models by intragastric administration of MO at the concentrations of 10, 20, 30, and 40 g per kg per d, respectively. After two weeks of medication, we observed the changes in the body weight, testicular and epididymal indexes, and microstructure of the testis tissue, measured the mean seminiferous tubule diameter (MSTD) , and obtained testicular biopsy scores (TBS) in different groups, followed by comparative analyses.

RESULTSAfter treatment, the CTX + NS group showed no remarkable differences in the body weight ([234.83 ± 28.77] g) and epididymal index (2.71 ± 0.34) from those of the four CTX + MO groups, but exhibited a significantly lower testicular index ([12.15 ± 1.04] g) than those in the CTX + 20 g/kg MO ([13.71 ± 0.97] g), CTX + 30 g/kg MO, ([13.30 ± 0.29] g), and CTX + 40 g/kg MO group ([13.48 ± 0.51] g) (P < 0.05). Light microscopy revealed obvious pathological changes of the testis tissue in the CTX + NS group and significantly ameliorated structures of the seminiferous tubules in the CTX + MO 10, 20, 30, and 40 g/kg groups, with the MSTD of (204.78 ± 11.03), (216.55 ± 10.93), (218.03 ± 11.23), and (218.59 ± 14.06) μm, respectively, and the TBS of 9.03 ± 0.39, 9.69 ± 0.26, 9.83 ± 0.18, and 9.89 ± 0.11, respectively, all significantly higher than (189.74 ± 8.55) μm and 5.95 ± 1.21 in the CTX + NS group (P < 0.05). The efficacy of MO extract was increased in a concentration-dependent manner.

CONCLUSIONMorinda officinalis extract can repair cytoxan-induced damage to rat spermatogenesis, with may achieve the best effect at the concentrations of 30 and 40 g per kg per d.

Animals ; Body Weight ; drug effects ; Cyclophosphamide ; toxicity ; Epididymis ; drug effects ; Male ; Morinda ; chemistry ; Mutagens ; toxicity ; Plant Extracts ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules ; drug effects ; pathology ; Spermatogenesis ; drug effects ; Testis ; drug effects ; ultrastructure

OBJECTIVETo estimate the reference value for micronucleus frequency of peripheral blood lymphocytes in general Chinese population, and to guide the genotoxicity evaluation and risk analysis for populations exposed to environmental or occupational chemicals.

METHODSA fulltext search was performed in CNKI with the key words of "micronucleus" and "human", and PubMed was searched with "cytokinesis-block micronucleus","CBMN","humans", and "adults", to obtain the articles published at home and abroad from 2001 to 2014 in which cytokinesis-block micronucleus (CBMN)assay was applied for micronucleus detection and populations not exposed to genotoxins were established as a control. Monte Carlo simulation was performed based on the micronucleus frequency, standard deviation, and sample size provided in these articles to calculate the micronucleus frequency for general population and to analyze the influence of sex, smoking, and drinking on micronucleus frequency.

RESULTSA total of 23 articles were included in the final analysis. The minimum mean micronucleus frequency was 0.39‰, and the maximum mean micronucleus frequency was 25.3‰. There were 1623 subjects in the control group in total (range 22~178, mean 70.6). Monte Carlo simulation was performed 100 times, and the mode of micronucleus frequency was 0 or 1‰; the values of P0, P25, P50 , P75, and P95 were 0‰, 1‰, 2‰~3‰, 5‰~6‰, and 14‰~19‰, respectively; the mean value was 4.36‰(range 4.22‰~4.57‰). With the application of one-sided 95% range(x±1.64 s), the upper limit of the range of reference value was calculated to be 13.46‰~14.75‰.

CONCLUSIONThe micronucleus frequency of peripheral blood lymphocytes in general Chinese population is 4.36‰, the interquartile range is 1‰~5‰ or 1‰~6‰, and the upper limit of reference value is 14.17‰. The factors of living area, sex, smoking, and drinking may influence micronucleus frequency.

Adult ; Alcohol Drinking ; DNA Damage ; Environment ; Humans ; Lymphocytes ; pathology ; Micronucleus Tests ; Monte Carlo Method ; Mutagens ; Reference Values ; Sex Factors ; Smoking

This study is designed to evaluate antioxidant and antigenotoxic activities of corn tassel extracts (CTTs). The major bioactive components of CTTs include flavonoid, saponin and polysaccharide. The antioxidant properties of the three bioactive components of CTTs were investigated by Ferric Reducing Antioxidant Property (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assays. The activities of the extracts were determined by assessing the inhibition of mutagenicity of the direct-acting mutagen fenaminosulf, sodium azide, and indirect-acting mutagen 2-aminofluorene using the Ames test (strains TA98 and TA100). The results showed that the extraction rates of flavonoid, saponin, and polysaccharide from the dried corn tassels were 1.67%, 2.41% and 4.76% respectively. DPPH and FRAP assay strongly demonstrated that CTTs had antioxidant properties. CTTs at doses of 625, 1250 and 2500 μg per plate reduced 2-aminofluorene mutagenicity by 12.52%, 28.76% and 36.49% in Salmonella typhimurium TA98 strain assay respectively and by 10.98%, 25.27% and 37.83%, at the same doses in Salmonella typhimurium TA100 assay system, respectively. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the different concentrations of CTTs inhibited the proliferation of MGC80-3 cells in a dose-dependent manner (P<0.01). It is concluded that these integrated approaches to antioxidant and antigenotoxicity assessment may be useful to study corn tassel as a natural herbal material.
Antimutagenic Agents ; pharmacology ; Antioxidants ; pharmacology ; Biphenyl Compounds ; antagonists & inhibitors ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Flavonoids ; pharmacology ; Fluorenes ; pharmacology ; Free Radical Scavengers ; pharmacology ; Humans ; Inflorescence ; chemistry ; Mutagens ; pharmacology ; Picrates ; antagonists & inhibitors ; metabolism ; Plant Extracts ; pharmacology ; Polysaccharides ; pharmacology ; Salmonella typhimurium ; drug effects ; genetics ; Saponins ; pharmacology ; Zea mays ; chemistry

OBJECTIVETo investigate the protective effect of epigallocatechin gallate (EGCG) on mouse sperm in vivo.

METHODSA total of 64 six-week-old male Kuming mice were randomly divided into eight groups of equal number to be treated with normal saline (negative control), Cyclophosphamide (CP) at 30 mg/kg (positive control), and CP followed by EGCG (experimental) at 20, 40, and 80 mg/kg, respectively, given every other day for 10 days. At 4 and 5 weeks after treatment, the bilateral testes of the mice were harvested for examination of sperm abnormality.

RESULTSEGCG did not increase the rate of CP-induced sperm abnormality in the mice, but reduced it instead with the prolonged time of treatment.

CONCLUSIONEGCG protects mouse sperm in vivo.

Animals ; Catechin ; analogs & derivatives ; pharmacology ; Cyclophosphamide ; toxicity ; Male ; Mice ; Mutagens ; toxicity ; Random Allocation ; Spermatozoa ; drug effects ; Time Factors

OBJECTIVEThe aim of this study was to investigate the use of the lesion-specific endonucleases-modified comet assay for analysis of DNA oxidation in cell lines.

METHODSDNA breaks and oxidative damage were evaluated by normal alkaline and formamidopyrimidine-DNA-glycosylase (FPG) modified comet assays. Cytotoxicity were assessed by MTT method. The human bronchial epithelial cell (16HBE) were treated with benzo (a) pyrene (B(a)P), methyl methanesulfonate (MMS), colchicine (COL) and vincristine (VCR) respectively, and the dose is 20 µmol/L, 25 mg/ml, 5 mg/L and 0.5 mg/L for 24 h, respectively. Oxidative damage was also detected by levels of reactive oxygen species in treated cells.

RESULTSFour genotoxicants give higher cytotoxicity and no significant changes on parameters of comet assay treated by enzyme buffer. Cell survival rate were (59.69 ± 2.60) %, (54.33 ± 2.81) %, (53.11 ± 4.00) %, (51.43 ± 3.92) % in four groups, respectively. There was the direct DNA damage induced by test genotoxicants presented by tail length, Olive tail moment (TM) and tail DNA (%) in the comet assay. The presence of FPG in the assays increased DNA migration in treated groups when compared to those without it, and the difference was statistically significant which indicated that the clastogen and aneugen could induce oxidative damage in DNA strand. In the three parameters, the Olive TM was changed most obviously after genotoxicants treatment. In the contrast group, the Olive TM of B(a) P,MMS, COL,VCR in the contrast groups were 22.99 ± 17.33, 31.65 ± 18.86, 19.86 ± 9.56 and 17.02 ± 9.39, respectively, after dealing with the FPG, the Olive TM were 34.50 ± 17.29, 43.80 ± 10.06, 33.10 ± 12.38, 28.60 ± 10.53, increased by 58.94%, 38.48%, 66.86% and 68.21%, respectively (t value was 3.91, 3.89, 6.66 and 3.87, respectively, and all P < 0.05), and the correlation between Olive TM and reactive oxygen species was better than other parameters (r = 0.77, P < 0.05).

CONCLUSIONThis study indicates that FPG-comet assay appears more specific for detecting oxidative DNA damage induced by genotoxicants exposure, and the application of comet assay will be expanded. The endonuclease modified comet assay will be used widely in the toxicology and molecular epidemiology study.

Cell Line ; Comet Assay ; methods ; DNA Damage ; Endonucleases ; Humans ; Mutagens ; toxicity ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; metabolism

INTRODUCTION: Chromosomal mutations are casual events in neoplasia development. Biomarker cytogenetic assays can determine exposure to mutagenic agents in occupational settings. This study assessed early biological marker chromosomal aberrations among health workers in the chemotheraphy oncology wards/ clinics, exploring its association to the subjects' occupational, environmental and baseline profile.
METHODS: This was an IRB approved cross-sectional exploratory study among hospital personnel working in the chemotherapy oncology facility of a tertiary government hospital, who underwent structured interview and blood extraction for cytogenetic assay after informed consent. Study funds only permitted assay of 44 specimens of 144 planned sample size, hence, Stata 6.0 only analyzed data from 44 subjects.
RESULTS: All 44 subjects had varying exposure to chemotherapy drug infusions. Of these, 79% had 1.0 breaks per cell (hypersensitive). Predominantly chromatid breaks (CTB), chromatid gaps (CTG), sister chromatid exhanges (SCE) were seen. No significant association was shown between mutagenic sensitivity and baseline characteristics, but with small sample size.
CONCLUSION: 21% borderline to hypersensitive mutagenic sensitivity among oncology workers at the tertiary government hospital is relatively significant, despite small sample size, connoting a must preventive promotive practice of chemotherapy administration in the workplace.

Human ; Male ; Female ; Chromosome Aberrations ; Chromosomes ; Drug Therapy ; Personnel, Hospital ; Cytogenetics ; Chromatids ; Mutagens