The probable reasons of arsenic susceptibility in a chronically exposed population of West Bengal.

Arsenic is potent human carcinogen which affects millions of people across the globe. Arsenic induced pre-cancerous and cancerous skin lesions are hall marks of chronic arsenic toxicity. Even then, only 15%-20% of the population manifest arsenic-induced skin lesions but the rest do not, the reason for which in not very clear. Not only that, conjunctival irritations of the eyes, peripheral neuropathy and respiratory distress are the non-dermatological health effects which are often manifested in them in addition to the cancers of skin and other internal organs. In this work we have considered 233 arsenic exposed individuals with skin lesions and 205 arsenic exposed individuals without skin lesions from the highly arsenic affected Murshidabad district of West Bengal. We have compared arsenic exposure in the two groups through drinking water. Both the study groups have similar levels of arsenic exposure, drinking same arsenic laden water. Results show that higher amounts of arsenic were retained in the nails and hair of the skin lesion group compared to the no skin lesion group. Significant higher amounts of chromosomal aberration and micronucleus formation were found in the skin lesion group, than the no skin lesion group. Incidences of conjunctival irritations of the eyes, peripheral neuropathy and respiratory distress were much higher in the former group compared to the later. We, thus found that one group was more susceptible than the other, even with similar levels of arsenic exposure. We have tried to identify and discuss the probable reasons for this observation with reference to our previous works in the exposed population from West Bengal, India.

Prenatal arsenic exposure induces immunometabolic alteration and renal injury in rats.

Arsenic (As) exposure is progressively associated with chronic kidney disease (CKD), a leading public health concern present worldwide. The adverse effect of As exposure on the kidneys of people living in As endemic areas have not been extensively studied. Furthermore, the impact of only prenatal exposure to As on the progression of CKD also has not been fully characterized. In the present study, we examined the effect of prenatal exposure to low doses of As 0.04 and 0.4 mg/kg body weight (0.04 and 0.4 ppm, respectively) on the progression of CKD in male offspring using a Wistar rat model. Interestingly, only prenatal As exposure was sufficient to elevate the expression of profibrotic (TGF-ß1) and proinflammatory (IL-1α, MIP-2α, RANTES, and TNF-α) cytokines at 2-day, 12- and 38-week time points in the exposed progeny. Further, alteration in adipogenic factors (ghrelin, leptin, and glucagon) was also observed in 12- and 38-week old male offspring prenatally exposed to As. An altered level of these factors coincides with impaired glucose metabolism and homeostasis accompanied by progressive kidney damage. We observed a significant increase in the deposition of extracellular matrix components and glomerular and tubular damage in the kidneys of 38-week-old male offspring prenatally exposed to As. Furthermore, the overexpression of TGF-ß1 in kidneys corresponds with hypermethylation of the TGF-ß1 gene-body, indicating a possible involvement of prenatal As exposure-driven epigenetic modulations of TGF-ß1 expression. Our study provides evidence that prenatal As exposure to males can adversely affect the immunometabolism of offspring which can promote kidney damage later in life.

Theaflavin-Containing Black Tea Extract: A Potential DNA Methyltransferase Inhibitor in Human Colon Cancer Cells and Ehrlich Ascites Carcinoma-Induced Solid Tumors in Mice.

Tea is the most popularly consumed beverage in the world. Theaflavin and thearubigins are the key bioactive compounds of black tea that have anticarcinogenic properties as reported in several studies. However, the epigenetic potential of these compounds has not yet been explored. DNA methyltransferase (DNMT) enzymes induce methylation of DNA at cytosine residues and play a significant role in epigenetic regulation and cancer therapy. The present study has explored the role of black tea as a DNMT inhibitor in the prevention of cancer. Herein, the effect of theaflavin has been studied in colon cancer cell line (HCT-116) and EAC-induced solid tumors in mice. It was found that theaflavin prevented cell proliferation and inhibited tumor progression as well. In silico study showed that theaflavin interacted with DNMT1 and DNMT3a enzymes and blocked their activity. Theaflavin also decreased DNMT activity In Vitro and In Vivo as evident from the DNMT activity assay. Results of immunohistochemistry revealed that theaflavin reduced DNMT expression in the tumors of mice. Taken together, our findings showed that theaflavin has a potential role as a DNMT inhibitor in HCT-116 cell line and EAC induced solid tumors in mice.

Antimutagenic and anticlastogenic effects of Turkish Black Tea on TA98 and TA100 strains of Salmonella typhimurium (in vitro) and mice (in vivo).

CONTEXT: Black tea has been reported to have significant antimutagenic and anticarcinogenic properties associated with its polyphenols theaflavins (TF) and thearubigins (TR). Similarly, Turkish black tea (TBT) also contains a considerable amount of TF and TR. OBJECTIVE: This study investigated the mutagenic, antimutagenic and anticlastogenic properties of TBT. MATERIALS AND METHODS: The mutagenic and antimutagenic effects of TBT (10 to 40000 µg/plate) were investigated in vitro on Salmonella strains TA98 and TA100 with and without S9 fraction. Anticlastogenic effect was studied at concentrations of 300-1200 mg/kg TBT extract by chromosomal aberrations (CA) assay from bone marrow of mice. RESULTS: The results of this study did not reveal any mutagenic properties of TBT. On the contrary, TBT extract exhibited antimutagenic activity at >1000 µg/plate concentrations in TA98 strain with and without S9 activation (40% inhibition with S9 and 27% without S9). In TA100 strain, the antimutagenic activity was observed at >20,000 µg/plate TBT extracts without S9 activation (28% inhibition) and at >1000 µg/plate with S9 activation (59% inhibition). A significant decrease in the percentage of aberrant cells (12.33% ± 1.27) was observed in dimethylbenz(a)anthracene (DMBA) plus highest concentration (1200 mg/kg) of TBT extract-treated group when compared to only DMBA-treated group (17.00% ± 2.28). DISCUSSION AND CONCLUSION: Results indicated that TBT can be considered as genotoxically safe, because it did not exert any mutagenic and clastogenic effects. As a result, TBT exhibited antimutagenic effects more apparently after metabolic activation in bacterial test system and had an anticlastogenic effect in mice.

Anticlastogenic effects of black tea polyphenols theaflavins and thearubigins in human lymphocytes in vitro.

Black tea accounts for nearly 80% of total World tea production. It contains dimeric flavanols and polymeric polyphenols known as theaflavins (TF) and thearubigins (TR). TR is exclusively present in black tea. On the basis of our previous potent antimutagenic and anticlastogenic effects of TF and TR in vitro in bacterial system and in vivo in mouse bone marrow cells, we have decided to extend our study in human cells in vitro. This study investigated the anticlastogenic effects of black tea polyphenols TF and TR as measured by chromosomal aberrations (CA) and micronuclei formation (MN) against two known mutagens/carcinogens i.e. benzo[a]pyerne (B[a]P) and aflatoxin B1(AFB1) with S9 activation. A significant decrease in both CA and MN were observed in the human lymphocyte cultures treated with either TF or TR pretreated with either B[a]P or AFB1 (250, 500, 1000 microg/ml) when compared with B[a]P or AFB1 treated cultures alone. TF shows more protective effects than TR in this in vitro system. These results indicate that both TF and TR have significant anticlastogenic effects in vitro in human lymphocytes.

Inhibition of benzo[a]pyrene induced mutagenicity and genotoxicity by black tea polyphenols theaflavins and thearubigins in multiple test systems.

This study investigated the antimutagenic and anticlastogenic effects of black tea polyphenols, theaflavins (TF) and thearubigins (TR) in Salmonella assay in vitro and in vivo in bone marrow cells of mice as measured by chromosomal aberrations (CA) and sister chromatid exchange (SCE) against a known carcinogen, benzo[a]pyrene (B[a]P). A significant decrease in mutagenicity in Salmonella assay and both CA and SCE were observed in all the different concentrations of TF and TR plus B[a]P treated series when compared with B[a]P treated group alone. These results indicate that both TF and TR have significant antimutagenic and anticlastogenic effects.