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Biomedical subjects

B H Xu

Publications and source records attributed to B H Xu.

9 recordsLinked to original sources
PubMed1992

Effect of buthionine sulfoximine and ethacrynic acid on cytotoxic activity of mitomycin C analogues BMY 25282 and BMY 25067.

BMY 25282 and BMY 25067, analogues of mitomycin C (MMC), were synthesized in an attempt to increase the therapeutic potential of the parent drug. The present studies were undertaken to determine if the cytotoxicity of MMC or its analogues is affected by cellular glutathione (GSH) and/or GSH transferase (GST) levels by using sensitive (P388/S) and multidrug resistant (P388/R-84) mouse leukemia cells as a model. P388/R-84 cells were cross-resistant to all three drugs. BMY 25067 was > 100 times more cytotoxic than MMC in both the cells. MMC and BMY 25282 produced significantly lower DNA interstrand cross-links (ISC) in P388/R-84 cells, whereas BMY 25067 induced ISC formation was comparable in these cells. GSH depletion with D,L-buthionine-S,R-sulfoximine (BSO) increased sensitivity to MMC, BMY 25282, and BMY 25067 by 3.4-, 4.1-, and 1.8-fold, respectively, in the resistant cells. Pretreatment of P388/R-84 cells with a nontoxic concentration of ethacrynic acid (EA) (10 micrograms/ml for 1 h), an inhibitor of GST activity, also resulted in a significant increase in the cytotoxic activities of MMC and BMY 25282 (3.8- and 3.1-fold, respectively), but not of BMY 25067. Combined pretreatment of P388/R-84 cells with BSO and EA caused further increase in the cytotoxic activities of both MMC and BMY 25282. Potentiation of BMY 25067 cytotoxicity by combined BSO and EA pretreatments was similar to that observed by BSO pretreatment alone. The ISC formation by MMC and BMY 25282 were also increased significantly by BSO or EA pretreatment in these cells. Whereas BSO treatment increased BMY 25067 induced ISC formation, it was not affected by EA pretreatment. These results suggest that (a) a potentiation of the cytotoxic activity of MMC or BMY 25282 can be achieved by GSH depletion and/or GST inhibition, (b) the enhanced cytotoxicity may be caused at least in part by the increased formation of drug-DNA cross-links, and (c) the mechanism of BMY 25067 cytotoxicity may be different from the other two drugs. The results of the present study also suggest that BMY 25067 may be seriously considered for further clinical development because it is much more active than MMC, and unlike the parent drug cytotoxicity of BMY 25067 does not seem to be affected by GST levels, which have been suggested to play an important role in cellular resistance to several cancer chemotherapy drugs.

Animals↗
PubMed1992

Modulation of mitomycin C resistance by glutathione transferase inhibitor ethacrynic acid.

This study was undertaken to elucidate the mechanism(s) of cross-resistance (4.9-fold) to mitomycin C (MMC) in a multi-drug-resistant cell line, P388/R-84. Intracellular accumulation of MMC by sensitive (P388/S) and P388/R-84 cells was comparable. Despite a 32% reduction in NADPH cytochrome P-450 reductase activity (responsible for MMC activation) in P388/R-84 cells, the rate of MMC bio-reduction by sensitive and resistant cells was similar. These results suggested that MMC resistance in P388/R-84 cell line must depend on factors other than impaired drug accumulation or bio-activation. Recent studies suggest that glutathione transferase (GST) dependent drug detoxification also contributes to cellular resistance of a variety of alkylating agents. Even though overexpression of GST has been noted in some MMC resistant tumor cells, it is not known if its level affects sensitivity to MMC. We have, therefore, determined the effect of ethacrynic acid (an inhibitor of GST activity) treatment on MMC cytotoxicity in P388/R-84 cells, which have about 2-fold higher GST activity than P388/S cells. The IC50 value for the inhibition of GST activity in vitro by ethacrynic acid (EA) was 16.5 microM (5 micrograms/ml). A depletion in intracellular GSH was also observed by treating P388/R-84 cells with EA alone or in combination with MMC. A non-toxic concentration of EA (1 microgram/ml; 3.3 microM) increased MMC cytotoxicity by 36% in P388/R-84 cells. MMC cytotoxicity was increased 2-fold by EA treatment in glutathione (GSH)-depleted P388/R-84 cells. These results suggest that GST mediated drug inactivation may represent another important mechanism of MMC resistance.

Animals↗
PubMed1992

Potentiation of mitomycin C cytotoxicity by glutathione depletion in a multi-drug resistant mouse leukemia cell line.

This study was undertaken to elucidate the mechanism of cross-resistance to mitomycin C (MMC) in a multi-drug resistant mouse leukemia cell line (P388/R-84). The P388/R-84 cells were 6.2-fold more resistant to MMC as compared to the sensitive cells (P388/S). Since oxygen radical formation has been suggested to be important in MMC cytotoxicity, MMC-dependent peroxidation of membrane lipids (an index of oxygen radical formation) was compared in these cell lines. MMC-dependent lipid peroxidation was 2.56-fold higher using P388/S cell extract when compared to that of P388/R-84 cells. Depletion of cellular glutathione (GSH) levels in the resistant cells produced a 1.76-fold increase in MMC-dependent lipid peroxidation. MMC cytotoxicity was also increased significantly by GSH depletion in P388/R-84 cells. These results suggest that cellular resistance to MMC in P388/R-84 cells may, at least in part, be due to the reduced formation of oxyradicals in these cells.

Animals↗
PubMed1992

Allergic contact dermatitis in shiitake (Lentinus edodes (Berk) Sing) growers.

A 42-year-old female shiitake grower was investigated to clarify the etiology of skin lesions which developed during the planting of shiitake hyphae into bed logs. She complained of repeated eczematous skin lesions during the planting season, from March to July, for 10 years. She handled 7,000 pieces of small conic blocks made of beech, with shiitake hyphae attached to their surface, per day, and 300,000 pieces altogether per season. She was positive on patch testing with extracts of shiitake hyphae. In contrast, female shiitake growers with skin lesions associated with work other than planting, and without skin lesions, were negative on patch testing to the hyphae. Moderate allergenicity was observed to extracts of shiitake hyphae in a guinea pig maximization test. These findings indicated the etiology of skin lesions in shiitake growers to be allergic contact dermatitis induced by shiitake hyphae.

Adult↗
PubMed1990

Temporal order and tactile patterns.

Temporal order judgments (TOJs) were obtained for tactile stimuli presented to subjects' fingerpads. In one set of measurements, pairs of spatial patterns were presented successively to a single fingerpad (same-site condition), to two fingers on the same hand (ipsilateral condition), or to two fingers on opposite hands (bilateral condition). The subjects were instructed to report which one of the two patterns was presented first. TOJs were more accurate in the same-site condition than in either the ipsilateral or the bilateral conditions. In the ipsilateral and bilateral conditions, performance improved when judging which one of two locations received a stimulus first, although performance levels were still lower than in the same-site condition. Increasing the size of the pattern set from which the two patterns to be judged were drawn had only a slight effect on same-site performance and no effect on ipsilateral/bilateral performance; however, changing the nature of the patterns had a considerable effect on same-site performance and a smaller effect on ipsilateral/bilateral performance. Introducing an intensity imbalance between members of the pair of stimuli also had a large effect on same-site TOJs: a less intense stimulus tended to be judged as being presented first. In the bilateral condition, however, there was a small effect in the reverse direction: more intense stimuli tended to be judged as being presented first. The intensity imbalance had no effect in the ipsilateral condition. The results suggest that different mechanisms are responsible for TOJs for patterns presented to the same-site and to separate sites and, furthermore, that separate sites may constitute separate channels for spatial information.

Adult↗
PubMed1989

[In vitro effect of epirubicin on human esophageal carcinoma cell line (Eca 109)].

Epirubicin is toxic, even at low concentration, to human esophageal carcinoma cell line (Eca 109). The survival response of exponential population growth of cells is biphasic: n = 1, Do = 0.27 micrograms/ml for 1 hr in the most sensitive population; Do = 7.90 micrograms/ml for 1 hr in the more resistant population. There was rapid cell killing effect at a high concentration (10 micrograms/ml Epirubicin for 1 hr). Exposure of cultured Eca 109 cells to Epirubicin led to an accumulation of cells with DNA content of S and G2 phases. Morphologic changes were mainly confined in the nucleus but cytoplasm was also affected when higher drug concentration or longer exposure time were used. Effects of epirubicin on cell growth, cell survival and cell cycle progression is dependent on both drug concentration and the duration of exposure.

Cell Cycle↗
PubMed1988

Health survey among farmers exposed to deltamethrin in the cotton fields.

A health survey was conducted among spraymen exposed to 2.5% deltamethrin EC in the cotton fields. The subjects were exposed to deltamethrin at concentrations of 0.022-24.070 micrograms/m3 in respiratory zone air and of 0.013-0.347 micrograms/cm2 of skin contact. Results showed that one-half of the 44 subjects examined complained of itching and burning sensations on their faces. A few miliary red papules also appeared on the face of one subject but not sign of acute deltamethrin poisoning was evident on physical examination. There were no significant differences between the subjects examined and the controls in sodium, potassium, and urea contents in the serum, sodium potassium ATPase and serotonin in whole blood, and 3-methyl-4-hydroxymandelic acid and 5-hydroxyindoleacetic acid in the urine. Deltamethrin in the urine of spraymen was below the detection limit (0.20 microgram/liter) of the method used.

Adolescent↗
PubMed1985

Effects of cadmium on cadmium smelter workers.

The effects of cadmium on 65 workers in a cadmium-refining plant in the People's Republic of China were investigated. The average airborne cadmium oxide concentrations ranged from 0.004 to 0.187 mg/m3 at most worksites. Except for some vague symptoms and reports of anosmia, no significant abnormalities were found in the clinical examinations. The level of cadmium in the blood and urine was increased in the majority of the cadmium-exposed subjects. Nine cases (13.8%) with suspected or mild renal tubular damage were found in this study.

Adolescent↗