Soumitra Sen

Bio: Soumitra Sen is an academic researcher from University of Calcutta. The author has contributed to research in topics: Betel & Etoposide. The author has an hindex of 11, co-authored 28 publications receiving 658 citations. Previous affiliations of Soumitra Sen include Mario Negri Institute for Pharmacological Research & Central Drug Research Institute.

Programmed cell death: concept, mechanism and control

Abstract: Programmed cell death or apoptosis occurs under physiological conditions as a result of physiological effectors. It is a relatively slower process and requires active participation of the cell in the suicidal mechanism. Apoptosis is controlled by precise intrinsic genetic programme and may be induced by almost all those stimuli causing necrosis. The role played by the intensity in determining the death process and the underlying mechanism is imperfectly understood. Morphologically apoptotic cells appear as small condensed body. The chromatin is dense and fragmented, packed into compact membrane-bound bodies together with randomly distributed cell organelles. The plasma membrane loses its characteristic architecture and shows extensive blebbing. It buds off projections so that the whole cell may split into several membrane-bound apoptotic bodies. Significant chemical changes take place in the plasma membrane. This helps in recognition of the apoptotic bodies by phagocytes. At this moment it is unclear if all cells can undergo apoptosis or it is a characteristic of only some tissues which are predisposed to apoptotic death being directly under the control of hormones or growth factors. Experimental studies aimed at comparison of induction of apoptosis in cells of different origin are warranted to elucidate this point. Biochemically a pre-commitment step for induction of death programmation through macromolecular synthesis is essential for most systems. The double-stranded linker DNA between nucleosomes is cleaved at regular inter-nucleosomal sites through the action of a Ca2+, Mg(2+)-sensitive neutral endonuclease. Zinc is a potent inhibitor of the enzyme. Calcium probably plays a key controlling role in activation of the enzyme since prevention of Ca2+ increase prevents endonuclease activation. It is becoming evident that signal transduction through appropriate receptors control the Ca2+ flux in the cells. Most apoptotic cells require synthesis of RNA and proteins. Delay or abrogation of apoptosis by inhibition of macromolecular synthesis is well known. The dying cells show high mRNA levels for several enzymes. Several degradative enzymes become active. Regulatory proteins maintain control over the apoptotic cascade. At the molecular level, search has been initiated for the mammalian equivalents of the cell death (ced) gene. Activation of several specific genes is indicated. Specific expression of cell death-associated gene products (e.g. TRPM-2/SGP-2) has been reported in several unrelated apoptotic cell systems. Sequential induction of c-fos, c-myc and 70 kDa heat shock protein is reported. Studies demonstrate that certain genes must remain in a transcriptionally active demethylated state during programmed cell death. Recent evidences clearly indicate that apoptosis may be positively or negatively modulated by certain genes.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of clastogenic effects of nicotine by chlorophyllin in mice bone marrow cells in vivo

Abstract: The effect of chlorophyllin in modifying the clastogenic action of nicotine was tested in vivo on mice bone marrow cells. Nicotine, when administered by gavage, induced chromosomal aberrations in frequencies directly proportional to the dose. Maximum effects were recorded at 6 h after exposure. Chlorophyllin, when given alone, was not clastogenic even at the highest concentration (1.50 mg/kg body wt). Simultaneous administration of nicotine and chlorophyllin with even lower doses (1.25 and 0.77 mg/kg body wt) reduced the frequency of chromosomal aberrations to the normal level. Chlorophyllin alone, given 2 h before nicotine, however, did not counteract the effects of nicotine. The use of green plant parts in modifying the genotoxicity of different agents may be related to the protective action of chlorophyllin.

Increase in topoisomerase-II-mediated DNA breaks and cytotoxicity of VP16 in human U937 lymphoma cells pretreated with low doses of methotrexate.

Abstract: Pre-treatment with low, non-toxic concentrations (0.04 microM) of methotrexate (MTX) for 16 hr increased etoposide (VP16)-induced growth inhibition and cytotoxicity in the U937 human histiocytic lymphoma cell line. VP16 cytotoxicity was significantly potentiated when the drug was given for 2 hr immediately after MTX pre-treatment or between 2 and 4 hr or 4 and 6 hr after recovery from MTX pre-treatment. By 24 hr after recovery from MTX, no potentiation was evident. The increased cytotoxicity of VP16 was associated with an increase in drug-induced DNA breaks as assessed by the alkaline elution method after proteinase K digestion. The amount of DNA single-strand breaks (DNA SSB) increased when the drug was given 0, 2, and 4 hr after MTX pre-treatment. DNA SSBs induced by the drug between 6 and 24 hr after MTX pre-treatment were similar to those seen in cells without pretreatment. The amount of DNA double-strand breaks (DNA DSB) caused by VP16 increased significantly when the drug was given 4 hr after recovery from MTX pre-treatment. VP16-induced DNA DSBs were still higher 6 hr after MTX pre-treatment, but by 24 hr they were similar to those observed in MTX-untreated cells. Flow cytometric analysis showed that MTX pre-treatment was causing an accumulation of U937 cells at the G1-S boundary of the cell cycle. When MTX was removed, a wave of synchronization followed. Using Western blot electrophoresis and polyclonal antibodies to antitopoisomerase II, we found that MTX pre-treatment raised the cellular topoisomerase II content. Our findings suggest that the potentiation of VP16 cytotoxicity on U937 cells by low, non-toxic MTX pre-treatment is due to a larger fraction of S-phase cells containing a higher concentration of topoisomerase II, which is the putative target of VP16 action.