Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels

Objectives

The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible.

Methods

Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 μM 5 min before exposure to irradiation by 2 Gy of X-rays.

Results

The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity.

Conclusion

Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected.     

Evaluation of environmental genotoxicity by comet assay in Columba livia

The concentrations of recognized or suspected genotoxic and carcinogenic agents found in the air of large cities and, in particular, developing countries, have raised concerns about the potential for chronic health effects in the populations exposed to them. The biomonitoring of environmental genotoxicity requires the selection of representative organisms as “sentinels,” as well as the development of suitable and sensitive assays, such as those aimed at assessing DNA damage. The aim of this study was to evaluate DNA damage levels in erythrocytes from Columba livia living in the metropolitan area of Monterrey, Mexico, compared with control animals via comet assay, and to confirm the results via Micronuclei test (MN) and DNA breakage detection–fluorescence in situ hybridization (DBD–FISH). Our results showed a significant increase in DNA migration in animals from the area assayed compared with that observed in control animals sampled in non-contaminated areas. These results were confirmed by MN test and DBD–FISH. In conclusion, these observations confirm that the examination of erythrocytes from Columba livia via alkaline comet assay provides a sensitive and reliable end point for the detection of environmental genotoxicants.     

Chromosomal DNA damage in APOE ɛ4 carriers and noncarriers does not appear to be different

DNA damage may play a key role in promoting disease‐onset and accelerated disease progression in Alzheimer's disease (AD) by increasing the rates of neuronal cell death. The ?4 allele of the APOE gene is the best characterised genetic risk factor for AD, however, it is unknown if APOE ?4 carriers exhibit increased levels of DNA damage which may contribute to increased AD risk. 175 healthy participants (aged 34–67 years old) from South Australia were recruited into the study and provided a single blood sample for the isolation of peripheral blood lymphocytes, APOE genotyping and lymphocyte chromosomal DNA damage analysis using the Cytokinesis‐Block micronucleus cytome (CBMN‐Cyt) assay with the micronucleus index being the primary outcome measure. When compared to non‐APOE ?4 carriers, APOE ?4 carriers did not exhibit altered rates of i) cell division, represented by the nuclear division index (NDI, P = 0.372), ii) cell death as represented by apoptotic (P = 0.457) and necrotic (P = 0.393) frequencies and iii) chromosomal DNA damage as indicated by the number of micronuclei (MNi, P = 0.795), nucleoplasmic bridges (NPBs, P = 0.221) or nuclear buds (NBUDs, P = 0.293) scored in binucleated cells. In conclusion, although we and others have previously shown that rates of chromosomal DNA damage measured using the CBMN‐Cyt assay are elevated in individuals with cognitive impairment, in this South Australian cohort the frequency of genome instability is not substantially influenced by the presence of the APOE ?4 allele. Environ. Mol. Mutagen. 56:694–708, 2015. © 2015 Wiley Periodicals, Inc.     

Health Effects from Occupational Radiation Exposure among Fluoroscopy-Guided Interventional Medical Workers: A Systematic Review

A systematic review was conducted to provide an overview of the health effects of occupational radiation exposure from interventional fluoroscopy procedures on medical radiation workers. Among the 34 studies that met the inclusion criteria, most studies were cross-sectional (76%) and published after 2011 (65%) in a handful of countries. Although diverse outcomes were reported, most studies focused on cataracts. Radiation health effects were rarely assessed by risk per unit dose. Interventional radiation medical workers represent a small subset of the population studied worldwide. Further epidemiologic studies should be conducted to evaluate health outcomes among interventional radiation medical workers.     

Mutagenic and clastogenic properties of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone: a potent bacterial mutagen in drinking water

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was found to be a direct-acting mutagen in the Ames test for strains TA1535, TA1538, TA92, TA97, TA98, TA100 and TA102. The highest mutagenic response (approximately 13,000 revertants/nmol) was seen in strain TA100. The TA100 response was six- to tenfold higher than in TA98, TA97, and TA102, and 100- to 500-fold higher than in TA1535, TA92, and TA1538. The addition of a 9,000 x g supernatant fraction (S-9) from livers of polychlorinated biphenyl-treated rats, along with cofactors for NADPH generation, resulted in a 90% reduction in the TA100 mutagenicity. MX induced chromosomal aberrations in Chinese hamster ovary cells after 6-8 hr exposure without S-9 at a dose as low as 4 micrograms/ml, and after 2 hr exposure with S-9 at a dose of 75 micrograms/ml. The oral dose of MX lethal to 50% (LD50) in Swiss-Webster mice was determined to be 128 mg/kg. MX did not induce micronuclei in mouse bone marrow when administered by oral gavage at doses up to 70% of the LD50.     

Dietary folate deficiency enhances induction of micronuclei by arsenic in mice

Folate deficiency increases background levels of DNA damage and can enhance the genotoxicity of chemical agents. Arsenic, a known human carcinogen present in drinking water supplies around the world, induces chromosomal and DNA damage. The effect of dietary folate deficiency on arsenic genotoxicity was evaluated using a mouse peripheral blood micronucleus (MN) assay. In duplicate experiments, male C57Bl/6J mice were fed folate-deficient or folate-sufficient diets for 7 weeks. During week 7, mice on each diet were given four consecutive daily doses of sodium arsenite (0, 2.5, 5, or 10 mg/kg) via oral gavage. Over the course of the study the folate-deficient diet produced an approximate 60% depletion of red blood cell folate. Folate deficiency by itself was associated with small but significant increases in MN in normochromatic erythrocytes (NCEs) and polychromatic erythrocytes (PCEs). Arsenic exposure was associated with significant increases in MN-PCEs in both folate-deficient and folate-sufficient mice. MN-PCE frequencies at the 10 mg/kg dose of arsenic were increased 4.5-fold over vehicle control in folate-deficient mice and 2.1-fold over control in folate-sufficient mice. At the 5 and 10 mg/kg doses of arsenic, MN-PCE levels were significantly higher (1.3-fold and 2.4-fold, respectively) in folate-deficient mice compared to folate-sufficient mice. Very few MN from either control or treated animals in either experiment exhibited kinetochore immunostaining, suggesting that the MN were derived from chromosome breakage rather than from whole chromosome loss. These results indicate that folate deficiency enhances arsenic-induced clastogenesis at doses of 5 mg/kg and higher.     

Individual sensitivity to genotoxic effects of nickel and antimutagenic activity of ascorbic acid

Cytotoxicity of nickel compounds was studied by stimulating the repair synthesis of DNA and counting lymphocyte micronuclei in workers of smelting shop of copper-nickel sulfide processing plant. Nickel content in the organism was evaluated by its concentrations in hair. Therapy with ascorbic acid (1 g/day for 1 month) led to a significant decrease in the number of micronuclei. The number of micronuclei before and after ascorbic acid treatment varied within a wide range in different individuals.     

Induction of meiotic micronuclei in spermatocytes in vivo by aflatoxin B1: light and transmission electron microscopic study in Swiss mouse

Dietary aflatoxins produce a disease state known as aflatoxicosis, and disruption of spermatogenesis is one of its serious consequences. Towards finding the cellular targets in spermatogenic compartment for aflatoxin toxicity, aflatoxin B(1) (AFB(1)) was administered to 90-day-old Swiss mouse through i.p. route at a daily dose of 20mug per kg body weight for 7, 15, 35 and 45 days. The testis and epididymis were subjected to light- as well as transmission electron microscopic analysis. One of the newer observations was occurrence of meiotic micronucleate giant spermatocytes in seminiferous epithelium and epididymal lumen. The origin of these cells could be traced to imminent disruption of spindle apparatus during meiotic division of spermatocytes, resulting in lagging of chromosome bivalents or replicated univalents. Such chromosomes appeared to undergo condensation and become micronuclei. Thus, this study reports that aflatoxin exposure would result in generation of meiotic micronucleate giant spermatocytes.