Genotype Frequencies of Drug-Metabolizing Enzymes Responsible for Purine and Pyrimidine Antagonists in a Healthy Asian-Indian Population

Purine and pyrimidine antimetabolites are used to treat leukemias, autoimmune diseases, and solid tumors. Detection of slow metabolizers before administration of the drugs is necessary to prevent any subsequent drug toxicity. With this aim, we determined the frequencies of normal and slow alleles in our population. Polymorphisms in genes encoding cytidine deaminase (CDA), dihydropyrimidine dehydrogenase (DPYD), and thiopurine-S-methyltransferase (TPMT) were documented in 225 healthy volunteers. The polymorphisms typed included CDA*3, DPYD*2A, TPMT*2A, TPMT*3B, and TPMT*3C. Methods used for genotyping included standard PCR-RFLP and allele-specific PCR reactions. The frequencies were 0.44?% for DPYD*2A, 0.67?% for TPMT*3B, and 0.89?% for TPMT*3C. The CDA*3 and TPMT*2A alleles were not detected. Although these polymorphisms have been demonstrated to be associated with drug toxicity in other populations, they appear to be very rare in the adult Indian population.     

Arsenic-induced health effects and genetic damage in keratotic individuals: involvement of p53 arginine variant and chromosomal aberrations in arsenic susceptibility

In West Bengal, India, more than 6 million people are exposed to arsenic through drinking water. Chronic arsenic exposure results in several multisystemic non-cancerous as well as cancerous effects in humans. Among non-cancerous effects, arsenic-specific skin lesions, conjunctivitis, peripheral neuropathy and respiratory diseases are prominent. One of the major consequences of chronic arsenic exposure is keratosis, the precancerous state of skin cancer. The tumor suppressor protein p53 consists of a polymorphism proline72arginine reported to be associated with various types of cancers. Previously we have reported that the p53 codon 72 arginine (Arg) homozygous genotype is associated with the development of arsenic-induced keratosis. In the present study we have investigated the distribution of health effects and chromosomal aberrations (CAs) in the individuals with keratosis. We have compared individuals with keratosis with those without arsenic-induced skin lesions but drinking similar level of arsenic-contaminated water. Attempts have also been made to find out the association of the p53 risk genotype with health effects and chromosomal aberrations. This study comprises of 349 unrelated exposed individuals (162 individuals with keratosis and 187 individuals without arsenic-specific skin lesions) from highly arsenic-affected districts of West Bengal, India. The results showed that health effects (i.e. peripheral neuropathy, conjunctivitis and respiratory illness) and chromosomal aberrations were significantly higher in the keratotic group compared to individuals with no skin lesions. Moreover, individuals with the arginine homozygous genotype showed increased levels of chromosomal aberrations compared to individuals with other genotypes; however, we did not find any significant association of the risk genotype with health effects. This study suggests that individuals with keratosis are more susceptible to arsenic-induced health effects and genetic damage and that the arginine variant of p53 can further influence the repair capacity of arsenic-exposed individuals, leading to increased accumulation of chromosomal aberrations.     

Segregation characteristics of multiple chromosomes ofAzotobacter vinelandii

The genome ofAzotobacler vinelandii has been taggedin vivo with transposons. The cells have then been allowed to divide and the pattern of segregation of the genomes has been studied. The results suggest the presence of multiple (possibly identical) copies of the genome inA. vinelandii. Only a fraction of the total number of genomes seem to have been tagged with transposon and an equilibrium between alleles of the same gene with and without the transposon was evident during random segregation.     

Transcriptional regulation of nitrogen fixation genes by DNA supercoiling

DNA gyrase (ATP dependent topoisomerase type II, EC 5.99.1.3) was found to be essential for the expression of the Klebsiella pneumoniae nitrogen fixation gene cluster carried by plasmid pRD1 in Escherichia coli. In the absence of DNA gyrase activity, nitrogen fixation activity could be restored by providing a constitutively expressed nifA function in trans. Our results suggest that nif gene regulation by oxygen may be mediated through the alteration of the superhelical status of the promoter of the nifLA regulatory operon, in addition to the action of the nifL gene product.Communicated by J. Schell     

Organogenesis and plant regeneration in Taxus wallichiana (Zucc.)

We describe an efficient process for regeneration of Taxus wallichiana plants via shoot organogenesis from callus cultures derived from zygotic embryos. Zygotic embryos cultured on half strength Lloyd and McCown's basal medium supplemented with SH vitamin ((1/2) WPMSH), 0.5 mg l(-1) 6-benzyladenine (BA) in combination with 1.0-2.0 mg l(-1) 2,4-dichlorophenoxyacetic acid (2,4-D) or alpha-Napthaleneacetic acid (NAA) produced two morphologically distinct types of calli-compact, green callus (CG) and compact, yellow (CY) callus after 4 weeks of culture. Optimum frequency (63%) of adventitious shoot bud induction was achieved in CG callus (3.0+/-0.67 shoot buds per gram of CG callus) when cultured on (1/2) WPMSH basal medium supplemented with 2.5 mg l(-1) BA after 4 weeks. The inclusion of 1% activated charcoal (AC) to (1/2) WPMSH basal medium (shoot elongation medium) led to maximum shoot elongation (2.15 cms). Microshoots rooted in high frequency (40%) in MS basal medium in which the concentration of nitrates was reduced to one-fifth the normal concentration after 4 months of culture.     

Protective effect of Nelumbo nucifera (Gaertn.) against H2O2-induced oxidative stress on H9c2 cardiomyocytes

Molecular Biology Reports - Ischemic heart disease (IHD), a severe condition of myocardium facing impediment in the supply of basic needs for cellular metabolism is caused by atherosclerosis....     

Oxidant stress, anti-oxidants and essential fatty acids in South Indian vegetarians and non-vegetarians

Vegetarians are known to have a low incidence of cardiovascular diseases and lower blood pressure compared to non-vegetarians. The exact cause for this is not known. In the present study, it was found that, in general, vegetarians (female > males) have a higher concentrations of anti-oxidant enzymes: catalase and superoxide dismutase in their RBC membranes and lower levels of plasma lipid peroxides compared to non-vegetarians. Both male and female non-vegetarians were found to have a higher n-3/n-6 ratio compared to vegetarians. These results suggest that vegetarians have a higher anti-oxidant status and low levels of n-3 fatty acids. It remains to be seen whether this alterations in the oxidant and anti-oxidant status and n-3 concentrations explains the lower incidence of cardiovascular diseases and lower blood pressure in vegetarians.     

How one becomes many: blastoderm cellularization in Drosophila melanogaster

Embryonic development in Drosophila melanogaster begins with a rapid series of mitotic nuclear divisions, unaccompanied by cytokinesis, to produce a multi-nucleated single cell embryo, the syncytial blastoderm. The syncytium then undergoes a process of cell formation, in which the individual nuclei become enclosed in individual cells. This process of cellularization involves integrating mechanisms of cell polarity, cell-cell adhesion and a specialized form of cytokinesis. The detailed molecular mechanism, however, is highly complex and, despite extensive analysis, remains poorly understood. Nevertheless, new insights are emerging from recent studies on aspects of membrane polarization and insertion, which show that membrane components from intracellular organelles are involved. In addition, actin and actin-associated proteins have been heavily implicated while new evidence shows that microtubule cytoskeletal elements are mechanistically involved in all aspects of cellularization. This review will draw on both the traditional models and the new data to provide a current perspective on the nature of cellular blastoderm formation in Drosophila melanogaster.