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B K Bhuyan

Publications and source records attributed to B K Bhuyan.

At least 55 records · Page 3Linked to original sources
PubMed1981

Cell kill kinetics of several nogalamycin analogs and adriamycin for Chinese hamster ovary, L1210 leukemia, and B16 melanoma cells in culture.

Nogalamycin is an anthracycline antibiotic which was markedly cytotoxic in vitro and was active against several tumor systems in vivo. We compare here the lethality of several nogalamycin analogs against Chinese hamster ovary (CHO), mouse leukemia (L1210), and mouse melanoma (B16) cells in culture. 7-con-O-Methylnogarol (7-con-OMEN) was the most lethal of all the analogs tested. Thus, for CHO cells exposed for two hr to the drug, the 50% lethal doses of 7-con-OMEN, nogalamycin, and dis-nogamycin were 0.25, 2.7, and 5.8 micrograms/ml, respectively. In general, CHO cells were less sensitive than B16 or L1210 cells to most compounds. All compounds gave dose-survival curves which consisted of a shoulder region followed by a region of exponential decline in survival. The nogalamycin analogs nogalamycin, dis-nogamycin, 7-con-O-methylnogalarol, and 7-con-OMEN were selected for further study because of their greater lethality in vitro and antitumor activity in vivo. The lethality of these compounds was compared to that of Adriamycin. 7-con-OMEN was more toxic to CHO cells than was Adriamycin but was less toxic to B16 and L1210 cells. All of these compounds (except 7-con-O-methylnogalarol which was not tested) were more lethal to exponentially growing cells than to plateau-phase cells. The survival response after different periods of exposure to these drugs was compared. In order to make valid comparisons of the time-survival response to different drugs, the drug concentrations chosen were such that they were equitoxic after a two-hr exposure. Under these conditions, the order of lethality after long-term exposure (8 hr to 24 hr) was nogalamycin > dis-nogamycin > 7-con-OMEN, Adriamycin > 7-con-O-methylnogalarol. With all the drugs, the rate of cell death increased with increasing drug concentrations.

Animals↗
PubMed1980

Bacterial mutagenicity and mammalian cell DNA damage by several substituted anilines.

Several substituted alkyl- and haloanilines were tested for their ability to mutate Salmonella typhimurium and to damage the DNA of mammalian (V79) cells. These results were correlated with their reported carcinogenicity. Of 9 suspected carcinogens, 4 were bacterial mutagens and 4 (out of 7 tested) damaged DNA of V79 cells. The following compounds were weakly mutagenic (less than 150 revertants/mumole): 4-fluoroaniline, 2,3-, 2,4-, 2,5- and 3,4-dimethylaniline, and 2-methyl-4-fluoroaniline. The following compounds were strong mutagens: 2,4,5-trimethylaniline, 2-methyl-4-chloro-, and 2-methyl-4-bromo-, 4-methyl-2-chloro-, 4-methyl-2-bromo- and 2-ethyl-4-chloroaniline. The compounds which damaged DNA in V79 cells were: 2 methyl-4-chloroaniline, 2-methyl-4-bromoaniline, 2,4,5- and 2,4,6-trimethylaniline.

Aniline Compounds↗
PubMed1980

Lethality of nogalamycin, nogalamycin analogs, and adriamycin to cells in different cell cycle phases.

The drugs studied included nogalamycin and its derivative 7-con-O-methylnogalarol, dis-nogamycin and its derivative 7-con-O-methylnogarol, and Adriamycin. All of these drugs, especially at high doses, were lethal to cells in every phase of the cell cycle, indicating that they were not phase specific. However, there were significant differences in drug sensitivity of cells in different parts of the cell cycle. Nogalamycin and Adriamycin were most lethal to the cells in S phase, whereas cells in M, G1, and G2 were much less sensitive. In contrast, the nogalamycin derivative 7-con-O-methylnogalarol was almost equally lethal to cells in all phases of the cell cycle. dis-nogamycin was most lethal to cells in postmetaphase and in early S phase. Cells in mid- and late G1, late S, and G2 were much less sensitive. The pattern of sensitivity to 7-con-O-methylnogarol was different from that of dis-nogamycin. 7-con-O-Methylnogarol was most lethal to cells in early G1, S, and G2. Only cells in mid- and late G1 were much less sensitive to this drug.

Animals↗
PubMed1979

Kinetics of cell kill by hyperthermia.

A review of published reports showed that there was surprisingly good agreement between different authors on the heat sensitivity of a particular cell line. For several cell lines, there was a marked difference in the heat of inactivation above 43 degrees (deltaH = 148 kcal/mol) and below 43 degrees (deltaH = 365 kcal/mol). This may indicate different mechanisms of cell killing above and below this temperature. With all cell lines tested, M- and S-phase cells were much more heat sensitive than were G1 or G2 cells. The heat sensitivity of S-phase cells is in contrast to the resistance of these cells to X-rays. The effect of hyperthermia on cell progression is discussed. The possibility of greater sensitivity of neoplastic cells to hyperthermia as compared to normal cells seems very promising.

Animals↗
PubMed1978

A multi-end point in vitro system for detection of new antitumor drugs.

By utilizing new types of producing microorganisms and isolating these on rather unusual growth media, we hope to produce new classes of antitumor drugs. In the detection system, we included the highly sensitive L1210 in vitro assay. But be requiring additional antimicrobial activity, we were able to eliminate rather early most of the previously known drugs from further work-up. The screening protocol was arranged so as to detect antimetabolites of a few rationally selected compounds.

Animals↗
PubMed1978

Effects of chartreusin on cell survival and cell cycle progression.

Chartreusin was lethal to both L1210 and P388 cells in culture with 90% of the cells being killed after a 24-hr exposure to 1.1 and 2.6 microgram/ml, respectively. The lethality of the drug increased in direct proportion to dose and exposure time. Both L1210 and Chinese hamster ovary cells in S phase were more sensitive to the lethality of the drug than were their corresponding non-S-phase cells. L1210 cells were partially synchronized by exposing an asynchronous culture to [methyl-3H]thymidine (20 Ci/mmol) and Colcemid for 3 hr. Synchronous culture of Chinese hamster ovary cells was established by planting mitotic cells. The progression of cells through the cell cycle was studied with flow microfluorometry both in the presence of the drug and after the drug had been washed off. In the presence of chartreusin the progression of mitotic cells into G1 was not affected. The movement of G1 cells into S was slower, and the movement of G2 cells into mitosis was blocked. When the drug was removed, the G2 to M block persisted for at least 4 hr but the progression of G1 cells to S was no longer inhibited.

Animals↗
PubMed1977

Cell proliferation kinetics and drug sensitivity of exponential and stationary populations of cultured L1210 cells.

Drug sensitivity and cell cycle parameters of L1210 cells in culture in exponential (10(5) to 4 x 10(5) cells/ml) and plateau phase (greater than 8 x 10(5) cells/ml) of growth were compared. The percentage of cells in G1, S, and G2 + M for exponential and plateau-phase cultures was 24.1, 70.0, and 5.9, and 42.5, 45.6, and 11.9, respectively. These values correspond to those reported previously for early and late L1210 mouse leukemia cells. Cell survival (measured by cloning) after drug exposure showed that actinomycin D, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, chlorozotocin, and streptozocin were all equally lethal to cells in both phases, and 1-beta-D-arabinofuranosylcytosine, high-specific-activity (20Ci/mmole) [3H]thymidine, vincristine, daunomycin, adriamycin, and 5-fluorouracil were more lethal to exponential cells than to plateau-phase cells. The percentage kill by S-phase-specific agents such as 1-beta-D-arabinofuranosylcytosine and[3H]thymidine corresponded well with the percentage of cells in S. Finally, 1,3-bis(2-chloroethyl)-1-nitrosourea was more toxic to plateau cells than to exponential cells.

Amino Acids↗
PubMed1977

Partial synchronization of L1210 cells by 5-fluorouracil and its use in drug combinations.

When L1210 cells growing logarithmically were exposed for 8 hr to a nonlethal dose of 5-fluorouracil (FU) (0.25 microgram/ml), the percentage of cells in S phase increased from 74.9% in the asynchronous culture to 93% in the FU-treated culture. This resulted in increased cell-kill by S-phase-specific inhibitors [1-beta-D-arabinofuranosylcytosine (ara-C), 5-hydroxy-2-formylpyridinethiosemicarbazone] when they were added to a culture partially synchronized by pretreatment with FU. For example, 2 hr exposure to ara-C alone or ara-C plus FU (added simultaneously to asynchronous culture) gave 28.8 and 25.8% survival, respectively, compared to 6.8% survival when ara-C was added for 2 hr to the partially synchronized culture. Eight to 12 hr after FU removal, the culture became asynchronous, such that ara-C addition at this time did not result in increased cell-kill. Cultures pretreated with FU were also highly sensitive to vincristine and Adriamycin. Adriamycin acted synergistically with FU (after 8 hr pretreatment) in killing L1210 cells.

Animals↗
PubMed1977

Sensitivity of different cell lines and of different phases in the cell cycle to hyperthermia.

The sensitivity of different cell lines (Chinese hamster ovary, HeLa, L1210, and P388) to 43 degrees was compared Chinese hamster ovary and HeLa cells were much less temperature sensitive than were L1210 or P388 cells. This difference persisted even when HeLa and L1210 cells were grown in the same medium and suggested that this was an inherent difference between the cell lines. Of all the cell lines, 7-day L1210 ascites, maintained by transfer in mice, were the most sensitive. The greater sensitivity of these cells, as compared to 4-day L1210 ascites or cells in culture, may be explained by the difference in their growth stages. The 7-day ascites cells would be in stationary growth as compared to the exponentially growing 4-day ascites or the cells in culture. The temperature sensitivity of Chinese hamster ovary cells in different parts of the cell cycle was determined. Mid and late-S-phase cells were more sensitive than cells in mitosis or early S; G1 and G2 cells were the least sensitive. In a partially synchronized culture, the heat sensitivity of L1210 cells increased with increased percentage of cells in S phase.

Animals↗
PubMed1976

Cytotoxicity, mutations and DNA damage produced in Chinese hamster cells treated with streptozotocin, its analogs, and N-methyl-N'-nitro-N-nitrosoguanidine.

The activities of streptozotocin (SZ), three structural analogs of SZ, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in producing cytotoxicity, mutations to 8-azaguanine (8-AzG) resistance, and DNA damage (single-strand breaks) in V79 Chinese hamster cells have been examined. These three biological processes appear to be associated. MNNG was about 10(3) times more active on a molar basis than SZ, and the activities of the analogs fell within these extremes.

Cell Line↗
PubMed1976

The influence of serum components on the growth and mutation of Chinese hamster cells in medium containing 8-azaguanine.

Low concentrations (less than or equal 20 mug/ml) of 8-azaguanine are 1000 fold more toxic to V79 Chinese hamster cells in medium containing 10% dialyzed fetal calf serum than in medium containing 10% undialyzed serum. Serum enzyme activity that converts AG to nontoxic 8-azaxanthine degrades AG at the same rate, whether or not the serum is dialyzed. However, cytotoxicity results similar to those obtained with US were produced in medium containing DS and 2.5 mug of hypoxanthine (HX)/ml (DSH). Therefore, serum HX is considered to be responsible for the relatively low cytotoxicity of AG in medium containing US. Colonies that arose in medium containing AG were isolated and characterized. Those that remained resistant to AG (40 mug/ml) and sensitive to aminopterin in the presence of HX and thymidine (HAT) were considered mutants; non-mutants were sensitive to AG and resistant to HAT. Colonies isolated from medium containing DSH or US and low concentrations of AG were not mutants, but those from medium containing high concentrations (greater than or equal 30 mug/ml) of AG were mutants. Spontaneous and N-methyl-N-nitro-N-nitrosoguanidine induced mutants were detectable in medium containing DSH without replating the cells prior to adding AG (greater than or equal 30 mug/ml), but in order to detect MNNG induced mutations in medium containing DS replating was essential. In DS, the mutation frequency increased as an exponential function of the toxicity of MNNG, but remained two orders of magnitude lower than the induced mutation frequencies that occurred in DSH. HX, in DSH or US, produced profound effects, other than interference with AG toxicity, that distort the results of mutagenesis assays. To study mutation using AG resistance as the endpoint, it is essential to use dialyzed serum.

Azaguanine↗
PubMed1976

Mutagenicity of streptozotocin and several other nitrosourea compounds in Salmonella typhimurium.

The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.

Histidine↗
PubMed1976

Use of cell-cycle information in the preparation of drug combinations: results with cytosine arabinoside plus actinomycin D1,2.

Cytosine arabinoside (ara-C) plus actinomycin D acted synergistically in killing L1210 and DON cells. The time course of cell-kill by the combination was different from that seen for either drug alone. The results obtained (both with L1210 and synchronous DON cells) suggest that cells blocked in G1/S with continuing unbalanced growth are particularly sensitive to the combined action of ara-C and actinomycin D.

Animals↗