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In vivo genetic toxicology tests measure direct DNA damage or the formation of gene or chromosomal mutations, and are used to predict the mutagenic and carcinogenic potential of compounds for regulatory purposes and/or to follow-up positive results from in vitro testing. These tests are widely used and consume large numbers of animals, with a foreseeable marked increase as a result of the EU chemicals...
Manganese superoxide dismutase (MnSOD) acts as an antioxidant and protects cells from the harmful effects of reactive oxygen species. We investigated the relationship between the MnSOD Ala-9Val polymorphism and breast cancer. Genotypes of 250 cases and 330 controls were determined by use of PCR-RFLP. Compared with the MnSOD Val/Val genotype, the MnSOD Val/Ala or MnSOD Ala/Ala genotype was not significantly...
Phototherapy (PT) is the most widely used form of treatment for unconjugated hyperbilirubinemia. One possible harmful consequence of PT is of a genetic nature. High levels of bilirubin may lead to oxidative damage in newborns: photochemical reactions may produce toxic photoproducts, probably peroxides. In order to investigate this hypothesis further under in vivo conditions, DNA strand-break frequency...
In the first case-control study on pancreatic cancer conducted on 253 cases and 403 controls in the Czech Republic we observed that the GSTP1-codon 105 Val variant allele and the GSTT1-null genotype were associated with an elevated risk for pancreatic cancer (OR=1.38; 95%CI=0.96–1.97 and OR=1.56; 95%CI=0.93–2.61, respectively). Combination of GSTT1-null and GSTP1-codon 105 Val variants further increased...
Poly-hydroxylated C 60 fullerenols (C 60 (OH) n ) have attracted much attention in biomedical research, due to a variety of biological activities. However, the studies investigating the genotoxic effects of fullerenols are still insufficient. The aim of the present study was to analyze the genotoxic and antigenotoxic potential of fullerenol C 60 (OH) 24 . The...
In order to study the impact of incident ions on organism mutation, positively and negatively charged low-energy oxygen and hydrogen ions were implanted into the dry seeds of Arabidopsis thaliana using three different dosages. The effects of ion irradiation on peroxidase abundance, activity, isozyme patterns, and transcription were analyzed. The results showed that ion irradiation increases peroxidase...
Circadian clocks are molecular time-keeping systems that underlie daily fluctuations in multiple physiological and biochemical processes. It is well recognized now that dysfunctions of the circadian system (both genetically and environmentally induced) are associated with the development of various pathological conditions. Here we describe the application of high throughput screening approach designed...
In the present study, the genotoxicity of chlorpyrifos was evaluated in the Chinese toad by using Comet assay and Micronucleus test (MN), as the potential tools for the assessment of genotoxicity. The first step was determined by the acute toxicity of chlorpyrifos. Tadpoles were exposed to the series of relatively high concentrations of chlorpyrifos for 96h. LC 50 values at 24, 48, 72, and...
Our society expects safety assessment for drugs, chemicals, cosmetics, and foods, which to date cannot be achieved without the use of laboratory animals. At the same time, society aims at refining, reducing, and (ultimately) replacing animal testing. As a consequence, much effort is taken to establish alternatives, such as toxicogenomics-based risk assessment assays on cultured cells and tissues....
Methylphenidate hydrochloride (MPH), a widely prescribed pediatric drug for attention deficit hyperactivity disorder, induced liver adenocarcinomas in B6C3F1 mice exposed to 500ppm in feed for 2 years (Dunnick and Hailey (1995) [14]). In order to determine if the induction of liver tumors was by a mutagenic mode of action, groups of male Big Blue (BB) mice (B6C3F1 background) were fed diets containing...
The circadian timing system rhythmically controls behavior, physiology, cellular proliferation and xenobiotic metabolism over the 24-h period. The suprachiasmatic nuclei in the hypothalamus coordinate the molecular clocks in most mammalian cells through an array of circadian physiological rhythms including rest-activity, body temperature, feeding patterns and hormonal secretions. As a result, shift...
The micronucleus-centromere assay using a pan-centromeric probe was used to assess chromosomal damage in lymphocytes of 47 industrial radiographers occupationally exposed to low dose ionizing radiation and 47 controls. The influence of genotype of DNA repair genes (XRCC1 399 , XRCC3 241 and XPD 751 ) on micronuclei (MN) frequency was also investigated. Centromere negative micronuclei...
The effect of thymol (TOH), a dietary compound was investigated for its ability to protect against radiation-induced cytotoxicity in Chinese hamster lung fibroblast (V79) cells growing in vitro. Treatment of V79 cells with 25μg/ml of TOH prior to 10Gy gamma radiation resulted increase in the cell viability than that of radiation alone as evaluated by MTT assay. Similarly, there was a significant increase...
Radiation injury to the bone marrow is potentially lethal due to the potent DNA-damaging effects on cells of the hematopoietic system, including bone marrow stem cell, progenitor, and the precursor cell populations. Investigation of radiation genotoxic effects on bone marrow progenitor/precursor cells has been challenged by the lack of optimal in vitro surrogate organ culture systems, and the overall...
Polymorphisms in DNA repair genes may be associated with altered DNA repair capacity, thereby influencing an individual's susceptibility to smoking-related cancers such as bladder cancer. Therefore, we sought to examine the correlation between single nucleotide polymorphisms in DNA repair genes and bladder cancer.We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250...
Breast cancer incidence increases rapidly as societies industrialize. Many changes occur during the industrialization process, one of which is a dramatic alteration in the lighted environment from a sun-based system to an electricity-based system. Increasingly, the natural dark period at night is being seriously eroded for the bulk of humanity. Based on the fact that light during the night can suppress...
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