Acrylonitrile ; toxicity ; Carcinogens ; toxicity ; Humans ; Mutagens ; toxicity ; Occupational Exposure

BACKGROUND: Fanconi's anemia (FA) is an autosomal recessive disease characterized by aplastic anemia, pre-malignancy, congenital malformations and chromosome breakage syndromes. As up to 30% of patients have no detectable congenital anomalies, the modern diagnosis of FA rests on chromosomal breakage of patient's cells induced by chemical clastogens such as diepoxybutane (DEB) or mitomycin-C (MMC). METHODS: We have done chromosome breakage test to differentiate FA from 11 aplastic anemia, three Diamond-Blackfan syndrome, three myelodysplastic syndrome, one acute leukemia with congenital anomaly and three siblings of FA. The peripheral blood lymphocytes from each individual were co-cultured in phytohemagglutinin-containing medium by the three methods, i.e., DEB treated, MMC treated and un-treated. RESULTS: Five cases were found to have increased chromosomal breakages to DEB and MMC, confirming diagnosis of FA. Other 21 cases showed no increased chromosomal breakages. No overlap was found between FA group and others (P<0.01). In one FA, there was no increased spontaneous breakage, but increased breakage to DEB and MMC. Of five FA, one case showed no congenital anomalies. CONCLUSIONS: Chromosme breakage test was shown to be simple, reliable and useful in ascertaining the diagnosis of FA.
Anemia, Aplastic ; Chromosome Breakage* ; Diagnosis* ; Fanconi Anemia* ; Humans ; Leukemia ; Lymphocytes ; Mitomycin ; Mutagens ; Myelodysplastic Syndromes ; Siblings

Xeroderma pigmentosum is autosomal recessive, degenerative disease generated by abnormal repair of DNA damaged by ultraviolet radiation and environmental mutagens. DeSanctis-Cacchione syndrome is the most severe form of xeroderma pigmentosum variant. This syndrome is characterized with microcephaly, progressive mental retardation and deterioration, retarded growth and sexual development, sensorineural deafness, and cerebellar ataxia, choreoathetsis, quadriparesis. We describe the case of a 17 year old female patient, which fits into Desanctis-Cacchione syndrome clinically.
Adolescent ; Cerebellar Ataxia ; Deafness ; DNA ; Female ; Humans ; Intellectual Disability ; Microcephaly ; Mutagens ; Quadriplegia ; Sexual Development ; Xeroderma Pigmentosum

Benzene ; poisoning ; DNA Damage ; DNA Repair ; genetics ; Deoxyguanosine ; analogs & derivatives ; genetics ; Humans ; Mutagens ; poisoning ; Poisoning ; genetics

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

Sister chromatid exchange (SCE) has recently become a common cytogenic assay system for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to have been exposed to such agents. A cross-sectional study of SCE frequency in peripheral blood lymphocytes from 45 Koreans aged 61 to 84 years was conducted. The effect of cigarette smoking and age on SCE was assessed by different degrees of smoking status such as smokers (n = 14), ex-smokers (n = 16) and non-smokers (n = 15). Mean spontaneous SCE per cell for the smokers (11.5 +/- 1.1) was significantly higher (p < 0.05) than that for the non-smokers (8.8 +/- 0.3). However, mean SCE frequencies per cell for the ex-smokers (10.3 +/- 0.6) were not significantly different from those of the smokers or the non-smokers. The smokers showed an increased number of high SCE frequency cells (HFCs) when compared to the ex-smokers and non-smokers (p < 0.05). The mean SCE frequencies of the non-smokers showed a statistically significant increase (p < 0.05) with the subject's age. These results show that age and smoking habits contribute a great deal in setting a higher degree of basal DNA damage in elderly Koreans, and smoking appeared to be a more significant damaging factor than age.
Aged* ; Carcinogens ; Cross-Sectional Studies ; DNA Damage* ; DNA* ; Humans* ; Lymphocytes* ; Mutagens ; Sister Chromatid Exchange ; Smoke* ; Smoking*

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

To assay the cytogenetic toxicity of NiCl, K2Cr2O7CdC12, and HgC12, the frequencies of sister chromatid exchanges(SCEs) and chromosomal aberrations were observed in the metaphase chromosomes of the human lymphocytes which were cultured with above materials. The frequencies of SCEs are dose-dependently increased by all materials in this experiment. Chromosomal aberrations, especially gap and break, are increased by the nickel and chromic compounds, while not significantly increased by the cadmium and mercurial compounds. This results indicate the dose dependent relationship between the frequencies of SCEs and the concentrations of the heavy metals, but the increasing rates of the SCEs induced by the heavy metals are less sensitive than other mutagens or carcinogens which were confirmed.
Cadmium ; Carcinogens ; Chromatids ; Chromosome Aberrations* ; Cytogenetics ; Humans ; Humans* ; Lymphocytes* ; Metals, Heavy* ; Metaphase ; Mutagens ; Nickel ; Siblings* ; Sister Chromatid Exchange*

Reciprocal exchanges of DNA in sister chromatids (SCEs) are induced by various carcinogens and mutagens, although the quantitative relationship between the number of mutations and SCEs induced varies among chemicals. Nevertheless, the analysis of SCEs production by various agents often proposed as a sensitive and quantitative assay for mutagenicity and cytotoxicity. Mercury, even if which has no evidences for mutagenicity and carcinogenicity, is reported to exert women cytotoxic effects, such as chromosomal aberrations or bad influences to ovulation and reproduction in experimental animals, etc. In this study, tests for sister chromatid exchanges have been carried out on normal human lymphocytes in whole blood culture to add mercury chloride (HgCl2) or methylmercury chloride(CH3 HgCl) for 72 hr. The results indicate the dose-dependent relationship between the frequencies of SCEs and the concentrations of HgCl2, CH3HgCl and 5-bromo-2-deoxyuridine (BrdU). Lymphocyte proliferation has depressed in the higher concentration of mercury.
Animals ; Carcinogens ; Chromatids ; Chromosome Aberrations ; DNA ; Female ; Humans ; Humans* ; Lymphocytes* ; Mercuric Chloride ; Mutagens ; Ovulation ; Reproduction ; Siblings* ; Sister Chromatid Exchange*

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