Biomonitoring of genotoxic effects among shielded manual metal arc welders.

Hexavalent chromium Cr (VI) used in shielded metal arc welding is widely recognized to act as a carcinogen, mutagen and teratogen. The carcinogenic potential of metals is a major issue in defining human health risk from exposure. Hence in the present investigation, 66 welders and 60 control subjects with similar mean ages, smoking prevalences and alcohol consumption were enrolled for DNA damage analysis of buccal cells by micronucleus (MN) and comet assay. Welders showed a significant increase in micronucleated cells compared to controls and a larger mean comet tail length. The current study thus suggested that chronic occupational exposure to Cr (VI) during welding could lead to increased level of DNA damage. Understanding the complexity of the relationships between exposure, basal DNA damage and MN frequencies requires larger scale studies and application of complementary biomarkers.

A novel polymorphism in BRCA2 exon 8 and breast cancer risk in South India.

In India the incidence of breast cancer is on the rise and it is rapidly becoming the number one cancer in females, pushing cervical cancer to the second spot. The contribution of BRCA2 to the development of the sporadic form of breast cancer remains undefined. To assess the role of SNPs in exon 8 of the BRCA2 gene in breast cancer development in India, a population-based study was here carried out on 107 breast cancer patients and 96 controls by PCR-RFLP and DNA sequencing. T-C transitions at positions 29 bp and 44 bp in relation to the total sequence of exon 8 were identified. Characterization of BRCA genes is relevant in a prevention setting as well as for the clinical management of hereditary breast cancer patients. The presently identified novel mutation in exon8 of the BRCA2 gene might have clinical significance.

Genotoxic effects of textile printing dye exposed workers in India detected by micronucleus assay.

The textile printing industry in South India employs a great number of workers that may possibly be exposed to toxic compounds. In the present study, subjects from textile printing units were investigated for the presence of genetic damage in their peripheral blood lymphocytes using micronucleus assay. Proliferation was also investigated using a nuclear division index. It was found that the micronucleus frequency was considerably greater in exposed subjects than in non exposed control subjects, but division was not increased in a statistically significant way. For the time being, this investigation should be considered as a preliminary study in which the influence of potential confounders could be adequately assessed. However, our results are non-ambiguous, indicating a potential health risk in these workers.

Enhanced calreticulin expression triggers apoptosis in the MCF-7 cell line.

Calreticulin, since its discovery as a ubiquitous protein of endoplasmic reticulum, has become recognized as a multifunctional luminal resident protein affecting many cellular functions ranging from development to death of a cell. However its role in cancer and significance for therapy remains to be clarified. Here to examine its effects, the calreticulin gene was over expressed in MCF-7 human breast cancer cell lines and influence on apoptosis was examined through an MTT assay. Upon culture in a suitable medium, cells transfected with the calreticulin gene were significantly more susceptible to apoptosis compared to controls. These findings therefore render a novel mechanism by which cancerous cells can be triggered to undergo death by upregulation of a protein resident in the lumen of the endoplasmic reticulum.

Evaluation of DNA damage induction and repair inhibition in welders exposed to hexavalent chromium.

The soluble hexavalent chromium Cr (VI) used in industrial welding is an environmental contaminant widely recognized to act as a carcinogen, mutagen and teratogen towards humans and animals. The carcinogenic potential of metals is a major issue in defining human health risk from exposure. In the present investigation, 93 welders and 60 control subjects with similar mean ages, smoking prevalences and alcohol consumption were enrolled for DNA damage analysis in blood leucocytes by Micronucleus assay (MN) and the Comet assay. DNA repair inhibition was also analyzed by assessing XPD gene polymorphism. Welders showed a significant increase in micronucleated cells compared to controls with respect to their smoking habits and alcohol consumption, age and years of exposure (P<0.05). Results indicated that the welders had a larger mean comet tail length than that of the controls (P<0.05). The current study suggested that chronic occupational exposure to Cr (VI) during welding could lead to increased levels of DNA damage and repair inhibition.

XRCC1399 and hOGG1326 polymorphisms and frequencies of micronuclei, comet and chromosomal aberrations among tobacco chewers: a South Indian population study.

DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agents such as those found in tobacco. Reduced DNA repair capacity may constitute a significant risk factor for cancers. Recently, a number of polymorphisms in several DNA repair genes have been discovered, these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility in exposed populations. In the present study, we explored the relationship between polymorphisms in the DNA repair gene XRCC1399 and hOGG1326 genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and risk of cancer development. 156 smokeless tobacco users and 70 controls without significant exposure to mutagens were recruited. Questionnaires were completed to obtain detailed occupational, smoking, and medical histories. A standard micronucleus assay, comet assay and chromosomal aberration assays were used as a marker of genetic damage. There were significant differences in the micronucleus (MN), Comet scores and chromosomal aberrations (CA) between smokeless tobacco users and control subjects by Student's t-test (P< 0.05). These findings provide evidence for the view that polymorphisms in DNA repair genes may modify individual susceptibility to tobacco related cancers and justify additional studies to investigate their potential role in development of cancer.