Damage to the genome is recognised as a fundamental cause of developmental and degenerative diseases. Several micronutrients play an important role in protecting against DNA damage events that are generated through endogenous and exogenous factors by acting as cofactors or substrates for enzymes that detoxify genotoxins as well as enzymes involved in DNA repair, methylation and synthesis. In addition it is evident that either micronutrient deficiency or excess can modify genome stability and that these effects may also depend on nutrient-nutrient and nutrient-gene interaction which is affected by genotype. These observations have led to the emerging science of Genome Health Nutrigenomics which is based on the principle that DNA damage is a fundamental cause of disease that can be diagnosed and nutritionally prevented on an individual, genetic sub-group or population basis. In this review the following topics are discussed: (i) Biomarkers used to study genome damage in humans and their validation; (ii) Current knowledge on micronutrients required for maintenance of genome stability in humans; (iii) Strategies to determine dietary reference values of single micronutrients and micronutrient combinations (nutriomes) based on DNA damage prevention.
The causes of lung cancer in northern Thailand have not been completely understood, but it is strongly believed that they are multi-factorial. The environmental and occupational factors have played a significant role on lung cancer. They can be categorized as physical, chemical, and biological. In the northern region of Thailand, specifically Chiang Mai province, it has been recognized that the incidence of lung cancer is among the highest in Thailand. For example, in the year 2007, the age-standardized incidence rate in males was 31.3 and that in female was 22.9 per 100,000 population. The district ranked the highest was Muang district, Chiang Mai. The previous studies showed that, apart from smoking, the indoor radon, air pollution and genetic factors might be the causes.
Chronic exposure to the toxic metalloid arsenic, either through occupational or environmental route results in the development of a plethora of dermatological as well as non-dermatological health effects, multi-organ cancers being the most severe ones. Several epidemiological studies have reported the occurrence of different types of cancers in populations exposed chronically to arsenic from different corners of the globe, but the spectrum of symptoms and severity vary widely. Several genetic and environmental factors might play an important causal role for such observed differences, including genetic polymorphisms, dietary habits and socio-economic status of the population. Unfortunately, the paradoxical nature of this carcinogen makes the use of animal model systems unsuitable, since they do not reflect the exact in vivo condition of arsenic exposure in human beings. Hence, in this present review, we have attempted to collate the isolated pieces of information available in existing literature depicting the various forms of arsenic-induced cancers, variations and etiology thereof. We have attempted to depict the entire spectrum of carcinogenic outcomes of chronic arsenic exposure and the interactions among several components like, genes (polymorphisms and mutations), environmental factors and dietary factors in the process. The literature reviews are primarily based on the human beings (in vivo), but to understand the underlying mechanism, we have also collated the information based on cell line models, and animal models where human data is scanty or unavailable. Thus, here we present a comprehensive review on the current state of research in the field of arsenic-induced cancer and explore the underlying mechanism of arsenic-induced carcinogenicity, along with relevant historical perspective.
Hepatocellular carcinoma (HCC) is one of the 5th most common cancers, with 80% of the cases occurring in low resource countries. Its etiology is dominated by complex interplay between chronic infection by hepatitis virus B or C (HBV, HCV), metabolic diseases and exposure to environmental carcinogens. In areas of high incidence of HCC, the most common risk factors are chronic HB carriage and exposure to a mycotoxin, aflatoxin B1 (AFB1), which contaminates many staples and causes mutations at the third base of codon 249 in the TP53 tumor suppressor gene in hepatocytes (R249S mutation). In this review, we summarize studies using a very sensitive and quantitative detection method, short-oligonucleotide mass analysis, to measure R249S in cell-free DNA isolated from the plasma of asymptomatic subjects and patients with chronic liver disease and/or HCC. These studies have identified that high levels of R249S were strongly associated with HBV-related HCC. Low to intermediate levels of R249S, in contrast, were detectable in asymptomatic subjects exposed to AFB1, with seasonal variations informative of the complex interactions between mutagenesis by AFB1 and chronic infection by HBV. Overall, we suggest that formation of R249S occurs in response to AFB1 exposure, well ahead of cancer development, thus generating large populations of cells at high risk for neoplastic transformation. In addition, R249S mutations may inactivate pro-apoptotic activities of p53 and contribute to rendering hepatocytes resistant to liver cell destruction by chronic inflammation, thus limiting chronic liver disease symptoms.
Egypt, as many other developing countries, has several environmental exposure problems. There are exposures to chemical genotoxicants and to lifestyle factors that have been linked to increased risk for cancer. Infections can be associated with cancer development when the environmental factors interact with the infection and lead to the enhancement of the carcinogenic process. Currently, there is a growing interest to genetic toxicology research, the use of different biomarkers and genetic susceptibility testing, which can contribute effectively to risk assessment. Developing countries need to cooperate with developed countries to protect human health from disease determined or influenced by factors in the environment. The national and international research policies should highlight the need to mobilize resources for human resource development, networking, improving research culture, information sharing and pragmatic use of research findings. Exchanging of experience and training is the most vital issues in developing new cadres of people with skills in health research, information and communication, who are needed to address the challenges facing the development of genetic toxicology research and prevention programs. Organizing international meetings and training courses may enforce this field of research and help to develop cooperative research projects which deal with different exposure conditions.
Capsaicin from the red chili pepper is a prospective chemopreventive agent. To explore the possible antigenotoxic effects of capsaicin on N-diethylnitrosamine (DEN)-induced mutagenesis in vitro, we conducted bacterial mutation assays with Salmonella typhimurium YG7108, a sensitive strain to mutagenic alkylating agents. Capsaicin was not mutagenic either with or without S9 activation. Unexpectedly,it enhanced the mutagenicity of DEN in the presence of S9 activation significantly. Capsaicin also enhanced the mutagenicity of 2-aminoanthracene and benzo[a]pyrene in the presence of S9 activation and benzo[a]pyrene diolepoxide in the absence of S9 activation. However, it reduced the mutagenicity of ethylnitrosourea in the absence of S9 activation. To examine whether capsaicin modulates DEN-induced mutagenesis and hepatocarcinogenesis in vivo, we took advantage of gpt delta rats, transgenic rodents that carry reporter genes for mutations. Female gpt delta rats were given drinking water containing 40 ppm DEN for five weeks. They were fed diets containing capsaicin at doses of 0, 100 or 500 ppm for seven weeks, starting one week before the DEN treatment. Samples were collected at weeks 7 and 32, respectively, for mutagenicity and carcinogenicity assays. DEN enhanced gpt mutant frequency more than 200 fold in the liver. However, capsaicin displayed no modulating effects on the mutagenesis. Rather, it reduced the number of liver neoplasms, especially liver cell adenomas, in a dose-dependent manner although the reduction in hepatocellular carcinoma was statistically insignificant. These results suggest that chemopreventive effect of capsaicin against DEN-induced hepatocarcinogenesis is slight and that the effect is not due to antimutagenesis. The results also caution that chemopreventive effects of chemicals should be examined not only in vitro but also in vivo with multiple indexes, e.g., in vitro and in vivo mutations and pathological examinations.
Genomic DNA is exposed to a constant insult from sources that are both endogenous and exogenous to the cell. REV1 protein, a eukaryotic member of Y family of DNA polymerases, is involved in the tolerance to such DNA damages by providing a translesion DNA synthesis. Here, we examined possible association between REV1 polymorphisms and breast cancer risk in Thai women. Five single nucleotide polymorphisms (SNPs) REV1 (rs3792152, rs3087395, rs3792137, rs959929, rs3087386) were genotyped. The study population consists of 570 patients with histopathologically confirmed breast cancer and 497 controls. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95%CI). Our results revealed that the heterozygote carrier of REV1 SNP (rs3087395) was associated with breast cancer risk with OR=1.59 (95%CI: 1.11-2.29). In addition, an increased risk was observed for homozygotes at the REV1 SNP (rs 959929) with the OR=1.52 (95%CI: 1.01-2.29). A stratified analysis suggested that the association between the REV1 SNPs and breast cancer is different by the menopausal status. The present results suggest that REV1 polymorphisms are likely to play a modifying role in the individual susceptibility to breast cancer among Thai women.