Endosulfan induces oxidative stress and changes on detoxication enzymes in the aquatic macrophyte Myriophyllum quitense

Endosulfan (1) is a chlorinated insecticide still in use in both developed and emerging countries. Although its toxicity on animals has been studied in the last years, scarce information is available on its effects on plants. In this study, we exposed the aquatic macrophyte Myriophyllum quitense to environmentally relevant concentrations of endosulfan (microg/L) (1) for a short time, simulating exposures that might occur after either accidental spills or toxic run-off from agricultural areas. The main goal was to evaluate changes in both detoxication and antioxidant enzymatic systems of this plant upon exposure to endosulfan (1). Thus, we measured the activities of catalase (CAT), soluble and membrane associated glutathione-S-transferases (s- and m-GSTs) and glutathione reductase (GR), as well as the hydrogen peroxide (H2O2) content. Results showed that endosulfan (1) exerts oxidative stress on M. quitense, which was evidenced by the increase of CAT activity and the H2O2 content in exposed plants. At 5 microg/L endosulfan (1), we found a generalized induction of activities of tested enzymes, indicating that this xenobiotic activates the protection system of this plant, increasing its capacity to scavenge reactive oxygen species. On the other hand, we did not find significant changes at 0.02 microg/L endosulfan (1), which is the maximal concentration allowed for freshwater. We conclude that runoff events, which can produce significant amounts of endosulfan (1) in aquatic environments during short time, can result in oxidative stress on M. quitense, and probably on similar macrophytes.     

GSTM1 and GSTT1 polymorphisms as modifiers of age at diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) in a homogeneous cohort of individuals carrying a single predisposing mutation

The variability in phenotype that occurs for so-called ‘single-gene disorders’ may be because of germline alterations in numerous primary and “modifier” genes. Within HNPCC families harbouring the same primary predisposing mutation, differences exist in the site of cancer, age of onset of disease symptoms and, consequently, survival until diagnosis of disease. The current study investigated a cohort of 129 individuals, from 13 different families, who harbour the identical nonsense mutation (C1528T) in the hMLH1 gene, predisposing them primarily to Lynch I syndrome. This cohort was screened for previously described polymorphisms in the glutathione-S-transferase genes, viz. GSTT1 and GSTM1. Male null carriers for both GSTT1 and GSTM1 were approximately three times more at risk of developing cancer at an earlier age when compared to non-null males. This work, particularly because of the relatively large “homogeneous” primary mutation cohort, provides evidence that genotypic changes distinct from the primary ‘HNPCC-causing’ mutation, influence the survival period until diagnosis of disease. It provides an impetus for expanding the study to include a wider range of candidate modifier genes. Such work may potentially lead to the development of individualised interval screening regimens for individuals with varying modifier genotypes—an attractive option in a resource-poor country.     

Bio-informatics based analysis of genes implicated in alcohol mediated liver injury

Alcohol induced liver injury has been studied extensively. Using literature search and bioinformatics tools, the present study characterizes the genes involved in alcohol induced liver injury. The cellular and metabolic processes in which genes involved in alcohol induced liver injury are implicated are also discussed. The genes related to alcohol induced liver injury are also involved in affecting certain molecular functions and metabolism of drugs, besides being associated with diseases. In conclusion, the changes in regulation of genes implicated in alcohol induced liver injury apart from causing alcohol mediated hepatic dysfunction may affect other vital processes in the body.