Search PubMed⌕ Search

Biomedical subjects

S Sircar

Publications and source records attributed to S Sircar.

32 records · Page 2Linked to original sources
PubMed1989

Lindane (gamma-HCH) causes reproductive failure and fetotoxicity in mice.

Lindane (gamma-Hexachlorocyclohexane) was orally given to pregnant Swiss female mice at various stages of pregnancy. During early pregnancy (1-4 days of gestation), the insecticide caused total absence of any implantation site, while given during mid pregnancy (6-12 days of gestation), lindane caused total resorption of fetuses. Lindane administration during late pregnancy (14-19 days of gestation) resulted in death of all pups either within 12 h (high-dosed group) or 5 days (low-dosed group) of parturition. Body weight of such pups were also highly reduced. When estrogen was given together with lindane at early pregnancy, implantation was normal, although subsequent fetal development was adversely affected. Progesterone, unlike estrogen, could not correct lindane-induced failure in implantation. On the other hand, when estrogen and progesterone were simultaneously given to lindane-fed mice during early pregnancy, both implantation and subsequent fetal development became comparable to normal mice. The insecticide besides being fetotoxic, thus appears to cause steroid hormone deficiency resulting in reproductive and developmental failure.

Animals↗
PubMed1989

Non-p-glycoprotein-mediated multidrug resistance in detransformed rat cells selected for resistance to methylglyoxal bis(guanylhydrazone).

Three independent variants (G2, G4, G5), resistant to methylglyoxal bis(guanylhydrazone), an anticancer drug, have been isolated by single step selection from an adenovirus-transformed rat brain cell line (1). These variants display selective cross-resistance to several natural product drugs of dissimilar structure and action. Multidrug resistance has recently been shown to be caused by overexpression of the membrane-associated p-glycoprotein, most often caused by amplification of the mdr gene. Several types of experiments were conducted to determine whether the observed drug resistance in our cell lines could be due to changes at the mdr locus. The following results were obtained: (a) the mdr locus was not amplified; (b) transcription of the mdr gene and p-glycoprotein synthesis were not increased; (c) multidrug resistance cell lines, which carry an amplified mdr locus, were not cross-resistant to methylglyoxal bis(guanylhydrazone); (d) verapamil did not reverse the resistance of G cells or mdr cells to methylglyoxal bis(guanylhydrazone), nor that of G cells to vincristine; and (e) methylglyoxal bis(guanylhydrazone) resistance was recessive and depended on a block to drug uptake, as opposed to mdr cells which are dominant and express increased drug efflux. The results obtained suggest that the drug resistance in the G2, G4, and G5 cells was atypical and may be due to a mechanism distinct from that mediated by the mdr locus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Normalization of epidermal growth factor receptor and transforming growth factor production in drug resistant variants derived from adenovirus transformed cells.

Variants (G2, G5) resistant to the cancer chemotherapeutic drug methylglyoxal bis (guanylhydrazone) (MGBG) were isolated from adenovirus type 2 transformed rat brain cells (F4; Sircar et al., 1987). Although at least one of these variants continued to express the adenovirus Ela and Elb transforming proteins, they both exhibited a detransformed phenotype as witnessed by flat morphology, loss of anchorage independent growth, and tumor forming capacity. Reverse transformation suggested the possibility of changes in growth factor receptors and the production of transforming growth factors. To test this possibility, we investigated the status of epidermal growth factor receptors (EGF-r) and transforming growth factor alpha (TGF-alpha) production in F4, G2 and G5 cells. The level of 125I-labeled EGF binding to intact drug resistant cells increased by 2- to 3-fold compared to the transformed parental cell. Scatchard analysis suggests that increased binding was the result of increased receptor levels rather than altered affinity of receptor for ligand. The production of growth factors which compete with 125I-labeled EGF binding declined in the detransformed G2 and G5 cells to a level intermediate between transformed (F4) and normal cells (FR3T3). EGF-receptor increase and the complementary decrease in growth factor production in the drug resistant variants may be associated with detransformation.

Adenoviridae↗
PubMed1988

Resistance to retransformation by adenovirus but not by heterologous oncogenes in an E1-positive transformation revertant cell line may be mediated by a cellular function.

Using an indirect selection method based on drug-resistance, we have previously reported the isolation of flat revertants from adenovirus 2 transformed rat cells. Here, we demonstrate that one of these revertants has suffered a mutation in a cellular effector gene specifically required for the adenovirus-mediated expression of the transformed phenotype. Evidence for this conclusion includes the following: (1) the cells contain a 16-times amplified copy of the E1 region, thus reducing the chances of viral mutations, (2) the cells synthesized E1a and E1b proteins indistinguishable from those of the transformed parent, (3) the mutation has been stable for over 2 years, and most importantly (4) the revertant was resistant to re-transformation by E1 but not by c-myc, N-ras or polyoma middle t oncogenes.

3T3 Cells↗
PubMed1987

Isolation and uptake characteristics of adenovirus transformed cell revertants resistant to the antiproliferative effects of methylglyoxal bis(guanylhydrazone).

Four independent variant cell lines resistant to the toxic action of methylglyoxal bis(guanylhydrazone), an anticancer drug and inhibitor of polyamine synthesis, have been isolated by single step selection from an adenovirus type 2-transformed rat brain cell line. Drug-resistance was accompanied by loss of tumorigenic potential in athymic nude mice. MGBG resistance was attributable to decreased drug uptake.

Adenosylmethionine Decarboxylase↗
PubMed1987

Isolation of variants resistant to methylglyoxal bis(guanylhydrazone) from adenovirus-transformed rat cells.

It is presumed that proteins encoded by viral oncogenes interact with proteins encoded by cellular genes to bring about the transformed phenotype. To demonstrate the existence of such cellular genes we attempted to isolate mutants with a nontransformed phenotype from an adenovirus-transformed rat cell line (F4) which contains multiple copies of the transforming E1 region. F4 cells were mutagenized with ethyl methanesulfonate and variants resistant to the anticancer drug methylglyoxal bis(guanylhydrazone) were selected. The proportion of such variants was about one in 10(6) and increased 5-fold after mutagenesis. Two variant clones (G1 and G2) were isolated and characterized: they were 5-fold more resistant to methylglyoxal bis(guanylhydrazone); they had a stable phenotype; they showed decreased drug uptake; they had a reduced ability to grow in soft agar, low serum, and nude mice; there was no detectable change in the restriction pattern of integrated viral genes or in the expression of the E1a and E1b proteins. These properties suggest that selection for methylglyoxal bis(guanylhydrazone) resistance may result in the isolation of variants with phenotypic characteristics of nontransformed cells. It was likely that these variants were altered in a cellular function required for the maintenance of the transformed phenotype.

Adenoviridae↗
PubMed1985

Effect of lindane on cytology and cytochemistry of exfoliated vaginal cells.

Intraperitoneal injection of 5 mg or 10 mg per kg body weight of technical grade lindane twice weekly in Charles-Foster female rats induced marked disturbance of the estrous cycle, prolonging the proestrus phase considerably (5-7 times more compared to the normal) and thereby delaying ovulation. Exfoliated cells at proestrus are marked by high concentrations of glycogen, SDH and alkaline phosphatase while estrus is characterized by increased activity of acid phosphatase and mucopolysaccharides. Corresponding changes in the polysaccharides concentrations and enzyme activities of the exfoliated cells seen in the lindane treated rats were well correlated with disturbances of the cycle. The data suggest that lindane exerts an estrogen-like effect by inducing a temporary negative feedback on pituitary gonadotropin secretion.

Acid Phosphatase↗
PubMed1983

The data base management system alternative for computing in the human services.

The traditional incremental approach to computerization presents substantial problems as systems develop and grow. The Data Base Management System approach to computerization was developed to overcome the problems resulting from implementing computer applications one at a time. The authors describe the applications approach and the alternative Data Base Management System (DBMS) approach through their developmental history, discuss the technology of DBMS components, and consider the implications of choosing the DBMS alternative. Human service managers need an understanding of the DBMS alternative and its applicability to their agency data processing needs. The basis for a conscious selection of computing alternatives is outlined.

Computers↗
PubMed1977

Adsorption characteristics of volatile anesthetics on activated carbons and performance of carbon canisters.

The adsorption characteristics, such as the adsorption capacity, the nature of the mass transfer zone, and heats of adsorption, are important for evaluating the performances of carbon canisters for removal of waste anesthetic vapors. The adsorption capacities and the natures of the mass transfer zones were measured for halothane, methoxyflurane, enflurane, isoflurane, and trichloroethylene on Witcarb 965 activated carbon. In addition, adsorption capacities and heats of adsorption for nitrous oxide, cyclopropane and oxygen were measured on the same carbon. The data indicate that high adsorption capacities of dilute anesthetic vapors on this activated carbon permit the use of carbon canisters for removal of these volatile anesthetics from mixtures with oxygen or nitrous oxide. In contrast, high concentrations of anesthetics such as nitrous oxide and cyclopropane cannot be removed economically by disposable canisters. A simplified procedure using the "characteristic curve" concept and "LUB/equilibrium section theory" for approximate prediction of the adsorption capacities and evaluation of the performance of a canister is outlined.

Adsorption↗
PubMedDate not supplied

Transformation renders MDR cells more sensitive to polyunsaturated fatty acids.

A series of genetically related cell lines that express mdr genes but differ in their ability to form tumors has been challenged with gamma-linolenate and eicosapentaenoate to verify if the sensitivity of tumorigenic mdr cells to cytotoxic PUFAs differs from the sensitivity of non-tumorigenic mdr cells. The tumorigenic mdr cell lines were derived by transformation of their parental non-tumorigenic mdr cell line with myc and ras oncogenes. Four ras and five myc transformed cell lines were used for the estimation of clonal variability. The data as based on colony forming assays, showed that six out of nine of the tumorigenic mdr cell lines were more sensitive than the non-tumorigenic mdr cells. These results suggest that a tumorigenic phenotype renders mdr cells more sensitive to PUFAs and that PUFA supplementation either alone or in conjunction with existing forms of cancer therapy may have significant clinical implications.

Animals↗
PubMedDate not supplied

Differential sensitivity of tumorigenic and genetically related non-tumorigenic cells to cytotoxic polyunsaturated fatty acids.

A series of closely related rat brain cell lines that differ in their ability to form tumors has been used to investigate the selectivity of cytotoxic polyunsaturated fatty acids. The colony-formation ability of tumorigenic F4 cells was markedly reduced when the cells were challenged with GLA and EPA. In contrast, the non-tumorigenic revertants were less affected. All retransformed tumorigenic variants exposed to GLA were as sensitive as their parental tumorigenic cells and more sensitive than the non-tumorigenic clones. However, two out of three retransformed tumorigenic variants exposed to EPA were less sensitive than either the parental tumorigenic or non-tumorigenic clones. The addition of ferrous chloride to the culture medium increased the cytotoxicity of GLA in tumorigenic but not in non-tumorigenic variants. These results suggest that tumorigenicity per se is characterized by a high sensitivity to PUFAs exogenously administered at appropriate concentrations and that the sensitivity is fatty acid specific.

Animals↗