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PubMed1999

The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration.

OBJECTIVE: Sodium lauryl sulphate (SLS) is the most commonly used detergent in dentifrices. Recent reports have suggested that it may exacerbate conditions with compromised epithelial integrity. The aim of this study was to compare the effect of an SLS-free dentifrice and an SLS-containing dentifrice on recurrent oral ulceration (ROU). DESIGN: A double-blind crossover clinical trial was carried out during which subjects used an SLS dentifrice for 8 weeks and an SLS-free dentifrice for 8 weeks. Each phase was preceded by a 2-week washout period. SETTING: A UK dental teaching hospital. SUBJECTS AND METHODS: Forty-seven subjects completed the trial. They were all in the age range 10-62 years, had regularly recurrent oral ulceration reporting at least one to two ulcers per month and had normal levels of vitamin B12, ferritin and folate. MAIN OUTCOME MEASURES: The trial phases were compared for the following ulcer parameters--number of ulcer days, total pain scores, number of ulcer episodes, and number of ulcers. Additional parameters compared were the number of ulcers per episode, ulcer duration, total pain per episode and ulcer size. RESULTS: None of the ulcer parameters measured was significantly affected by the use of the SLS-free dentifrice as compared with the SLS dentifrice. CONCLUSION: SLS-free dentifrice had no significant effect on ulcer pattern in the ROU study group.

Adolescent↗

PubMed2004

A new MLC segmentation algorithm/software for step-and-shoot IMRT delivery.

We present a new MLC segmentation algorithm/software for step-and-shoot IMRT delivery. Our aim in this work is to shorten the treatment time by minimizing the number of segments. Our new segmentation algorithm, called SLS (an abbreviation for static leaf sequencing), is based on graph algorithmic techniques in computer science. It takes advantage of the geometry of intensity maps. In our SLS approach, intensity maps are viewed as three-dimensional (3-D) "mountains" made of unit-sized "cubes." Such a 3-D "mountain" is first partitioned into special-structured submountains using a new mixed partitioning scheme. Then the optimal leaf sequences for each submountain are computed by either a shortest-path algorithm or a maximum-flow algorithm based on graph models. The computations of SLS take only a few minutes. Our comparison studies of SLS with CORVUS (both the 4.0 and 5.0 versions) and with the Xia and Verhey segmentation methods on Elekta Linac systems showed substantial improvements. For instance, for a pancreatic case, SLS used only one-fifth of the number of segments required by CORVUS 4.0 to create the same intensity maps, and the SLS sequences took only 25 min to deliver on an Elekta SL 20 Linac system in contrast to the 72 min for the CORVUS 4.0 sequences (a three-fold improvement). To verify the accuracy of our new leaf sequences, we conducted film and ion-chamber measurements on phantom. The results showed that both the intensity distributions as well as dose distributions of the SLS delivery match well with those of CORVUS delivery. SLS can also be extended to other types of Linac systems.

Algorithms↗

PubMed2000

Sodium lauryl sulfate increases the efficacy of a topical formulation of foscarnet against herpes simplex virus type 1 cutaneous lesions in mice.

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.

Administration, Topical↗

PubMed2003

Cytotoxic effects of streptolysin o and streptolysin s enhance the virulence of poorly encapsulated group a streptococci.

Although the toxicity of streptolysin O (SLO) and streptolysin S (SLS) in purified group A streptococci (GAS) has been established, the effect of these molecules in natural infection is not well understood. To identify whether biologically relevant concentrations of SLO and SLS were cytotoxic to epithelial and phagocytic cells that the bacteria would typically encounter during human infection and to characterize the influence of cell injury on bacterial pathogenesis, we derived GAS strains deficient in SLO or SLS in the background of an invasive GAS M3 isolate and determined their virulence in in vitro and in vivo models of human disease. Whereas bacterial production of SLO resulted in lysis of both human keratinocytes and polymorphonuclear leukocytes, GAS expression of SLS was associated only with keratinocyte injury. Expression of SLO but not SLS impaired polymorphonuclear leukocyte killing of GAS in vitro, but this effect could only be demonstrated in the background of acapsular organisms. In mouse invasive soft-tissue infection, neither SLO or SLS expression significantly influenced mouse survival. By contrast, in a mouse model of bacterial sepsis after intraperitoneal inoculation of GAS, SLO expression enhanced the virulence of both encapsulated and acapsular GAS, whereas SLS expression increased the virulence only of acapsular GAS. We conclude that the cytotoxic effects of SLO protect GAS from phagocytic killing and enhance bacterial virulence, particularly of strains that may be relatively deficient in hyaluronic acid capsule. Compared to SLO, SLS in this strain background has a more modest influence on GAS pathogenicity and the effect does not appear to involve bacterial resistance to phagocytosis.

Animals↗

PubMed1989

Plaque inhibition by a combination of zinc citrate and sodium lauryl sulfate.

Bacteriological tests demonstrated an additive inhibitory effect of ZnCl2 and sodium lauryl sulfate (SLS) on in vitro growth of Streptococcus sobrinus OMZ 176 and of Streptococcus sanguis ATCC 10556. As measured by atomic absorption spectrophotometry, the solubility of zinc citrate increased in the presence of SLS. After 48 h, the concentration of solubilized zinc from aqueous solutions of 5.0 mM zinc citrate was 12.0 mM versus 14.4 mM in the presence of 34.7 mM SLS. The plaque-inhibiting properties of aqueous solutions of 12.0 mM Zn2+ from zinc citrate, 34.7 mM SLS, and 14.4 mM Zn2+ from zinc citrate in combination with 34.7 mM SLS were examined in 7 volunteers. Plaque accumulations were assessed by using a method earlier described after 3 days of twice daily mouthrinses with 10 ml test solution, during which period no mechanical oral hygiene was performed. Compared to placebo, SLS and zinc citrate increased the frequency of plaque index score 0 by 52.9 and 98.3%, respectively, and SLS gave 36.9% and zinc citrate 55.7% less surfaces with scores 2 or 3 (p less than 0.05 in all cases). The combination of zinc citrate and SLS gave a threefold increase of plaque index score 0 and a 70.5% reduction of scores 2 or 3 (p less than 0.05).

Chemical Phenomena↗

PubMed2006

Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast growth factor receptor 3.

Normal fibroblast growth factor receptor 3 (FGFR3) acts as a negative bone growth regulator by restricting chondrocyte proliferation and endochondral bone elongation. In sheep, a heritable mutation that inactivates FGFR3 produces skeletal overgrowth when homozygous, this condition is commonly referred to as spider lamb syndrome (SLS). We hypothesized that sheep heterozygous for the inactivated FGFR3 mutation (FGFR3(SLS/+)) would exhibit enhanced long bone growth and greater frame size; additionally, the isolated effects of increased bone growth would translate into greater BW and larger LM area relative to normal lambs at harvest. The current study investigated bone length and LM area of FGFR3(SLS/+) sheep at maturity and during growth. At maturity, FGFR3(SLS/+) ewes exhibited a larger frame size and longer bones than normal FGFR3(+/+) ewes (P < 0.05). Similarly, FGFR3(SLS/+) lambs had greater frame sizes than normal FGFR3(+/+) lambs, as indicated by increased metacarpal III length and height at withers (P < 0.05). The FGFR3(SLS/+) lambs took longer than the normal FGFR3(+/+) lambs to reach the 60-kg common BW harvest end point (P < 0.05). The FGFR3(SLS/+) lambs showed no difference in BW, ADG, or LM area at any age compared with normal FGFR3(+/+) lambs (P > 0.2). A similar LM area produced in the context of a greater frame size and skeletal length produces a greater muscle volume, thereby potentially increasing meat yield. The results of this study suggest that FGFR3(SLS/+) animals exhibit a relaxation of the normal inhibition of chondrocyte proliferation, resulting in an increase in the overall frame size. The sheep industry could utilize the naturally occurring genetic mutation in FGFR3 to potentially increase meat yields with enhanced skeletal growth as an alternative to exogenous growth promotants.

Aging↗

PubMed2003

The effects of two sodium lauryl sulphate-containing toothpastes with and without betaine on human oral mucosa in vivo.

The aim was to compare the effects of two sodium lauryl sulphate (SLS)-containing toothpaste formulations with and without betaine on human oral mucosa in vivo. The results are compared with the effect of a dry mouth toothpaste without SLS. Twenty subjects participated in the double blind, crossover study. The toothpastes with 1.2% SLS, 1.2% SLS and 4% betaine and with 4% betaine but not with SLS were placed on buccal mucosa in a test chamber and kept in place for 15 min. The condition of the mucosa was studied both visually and using electrical impedance (EI) for up to 45 min. Both SLS-containing pastes had a similar, irritating effect on the mucosa as judged both by the appearance of the mucosa and the EI measurements. The dry mouth toothpaste (with betaine only) showed no significant irritation of the mucosa. Betaine did not reduce the mucosa-irritating effect of the SLS-containing toothpaste formulation. The surfactant-free toothpaste did thus not irritate the human oral mucosa in vivo while the SLS-containing pastes did.

Adult↗

PubMed2003

Primary insertion of a silastic spring-loaded silo for gastroschisis.

Gastroschisis is traditionally managed by emergency primary closure, with a temporary silo reserved for large defects unable to be closed primarily. We recently have begun primary Silastic (Dow Coming, Midland, MI) spring-loaded silo (SLS) closure followed by elective closure and report our preliminary experience. A total of 15 infants (weight range, 2.1-13.5 kg) at 2 different institutions were treated by SC by 3 different surgeons between 1998 and 2002. A 3-, 4-, or 5-cm (ring diameter) silo was used depending on size of abdominal wall defect. Elective closure was performed in the operating room or at the bedside. Surgical parameters assessed included success of SLS, peak inspiratory pressures (PIPs) pre- and post-SLS closure, total time of staged closure with SLS, time to full feedings, and intra- and postoperative complications. Fifteen of 15 infants were successfully treated by SLS closure followed by elective closure. Two of 15 (13.3%) experienced temporary dislodgement of the silo prior to permanent closure. In both cases, the silo was safely reinserted at the bedside. Comparison of PIP values measured at various stages of SLS closure revealed no significant difference (P > 0.05). Mean times to final fascial closure (3.7 days) and full enteral feedings (22 days) were similar to historical controls obtained from the surgical literature. In 1 case where there was associated intestinal atresia, SLS closure was effective in permitting concomitant elective closure and re-establishment of bowel continuity. All children are alive and well at the time of this report. SLS closure permits safe, gentle, and gradual reduction of the exposed viscera leading to successful permanent abdominal wall closure. Respiratory embarrassment and hemodynamic instability associated with emergent (primary) closure of large abdominal wall defects can thus be avoided.

Digestive System Surgical Procedures↗

PubMedDate not supplied

pH influence of surfactant-induced skin irritation. A non-invasive, multiparametric study with sodium laurylsulfate.

Even though various experimental methods have been proposed for in vitro testing of detergents such as LSL (sodium laurylsulfate) no absolutely relevant clinical information can be inferred from them as to the irritancy of a given compound. In particular the relative importance of pH needs further assessment. This study reports on in vivo evaluation of skin function changes under given experimental conditions with SLS applied at 3 different pH values. There is a dramatic increase of transepidermal water loss (TEWL), i.e. a substantial reduction in the barrier function of the skin, when SLS is applied under occlusion for 48 H. The alkaline control solution (NaOH pH 9) induced low-grade, but significant TEWL increases, as compared to the other controls (distilled water pH 7; HCl pH 5), which had no influence on TEWL. The changes obtained with the controls were much lower than those observed with SLS. The barrier-function changes induced by the surfactant SLS could, however, promote transepidermal passage of acid and/or alkaline molecules, hence increasing toxic damage of the skin; yet no such effects could be observed, indicating that the main effects are due to detergency. Assessment of cutaneous blood flow values (CBFV) by laser Doppler velocimetry showed increased values after SLS. When pH-adjusted SLS solutions were compared, there was neither a difference in relation to pH nor did the control solutions induce any significant CBFV change. This study reveals that TEWL and CBFV are probably the most reliable methods to investigate acute irritancy by SLS. Accordingly, pH cannot be considered as a major contributive factor of irritancy when SLS solutions are applied under occlusion (48 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed2000

Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport.

Application of low-frequency ultrasound has been shown to enhance transdermal transport of drugs (low-frequency sonophoresis). In this paper, we show that the efficacy of low-frequency ultrasound in enhancing transdermal transport can be further increased by its combination with sodium lauryl sulfate (SLS), a well-known surfactant. The dependence of the ultrasound-SLS-mediated transport on ultrasound parameters, including intensity, net exposure time, and duty cycle, is discussed. The transdermal transport enhancement is proportional to ultrasound intensity as well as to exposure time, and is independent of duty cycle as long as the net exposure time is the same. The synergistic effect of SLS and ultrasound on transdermal transport increases linearly with SLS concentration. The enhancement is also proportional to the ultrasound energy density beyond a threshold value, which suggests that a certain minimum amount of energy density is required before noticeable changes in skin permeability occur. A similar dependence of the transdermal transport enhancement on energy density is observed in the case of the enhancement induced by ultrasound alone. Although the threshold energy density value in the presence of SLS is about 10 times lower than that in the case of ultrasound alone, the relationship between enhancement and energy density in the presence and in the absence of SLS is otherwise similar. Possible mechanisms for the synergistic effect of ultrasound and SLS are also discussed.

Aluminum↗

PubMed1994

Bioavailability of cefuroxime axetil formulations.

Cefuroxime axetil tablets have proved effective for the treatment of a variety of community-acquired infections. A suspension formulation has been developed for use in children. Two studies have been conducted to determine if the cefuroxime axetil formulations are bioequivalent. In the initial randomized, two-period crossover study, 24 healthy men received 250-mg doses of suspension and tablet formulations of cefuroxime axetil every 12 h after eating for seven doses. Each treatment period was separated by 4 days. Comparisons of serum and urine pharmacokinetic parameters indicated that the suspension and tablet formulations of cefuroxime axetil are not bioequivalent. Following the initial bioequivalency study, 0.1 % sodium lauryl sulfate (SLS) was added to the suspension to assure the homogeneity of the granules during the manufacturing process. In the subsequent randomized, three-period crossover study, 24 healthy men received single 250-mg doses of three cefuroxime axetil formulations: suspension without SLS, suspension with SLS, and tablet. Again each treatment period was separated by 4 days. Pharmacokinetic analyses demonstrated that while the suspension with SLS and suspension without SLS are bioequivalent, bioequivalence between the suspension with SLS and the tablet was not observed. Thus, the addition of the SLS surfactant to the suspension did not alter the bioavailability of the formulation.

Adult↗

PubMed1999

Cytochrome P-450 content and activity after cold storage of rat hepatocytes in university of wisconsin and sodium-lactobionate-sucrose solutions.

We compared the capacity of University of Wisconsin (UW) and of sodium-lactobionate-sucrose (SLS) hypothermic preservation solutions to maintain the integrity of the hepatic cytochrome P-450-dependent mono-oxygenase system. Isolated rat hepatocytes were stored for 0, 10, 24, and 48 hours in UW or SLS solution and were subsequently cultured shortly at 37 degrees C. Cell viability declined slightly but significantly in a time-dependent manner during cold preservation in either UW or SLS solution, and warm culture exacerbated this effect. Total cytochrome P-450 declined gradually after cold preservation and warm culture to reach values of 70% and 52% of unstored controls in cells preserved for 24 and 48 hours in cold UW solution, respectively. Storage in cold SLS solution yielded a similar decrease to 79% and 59% of unstored controls for the equivalent preservation times. Cytochrome P-450 activity was assessed by the metabolism of theophylline after various cold preservation times in UW or SLS solutions. Production of the major metabolite 1,3-dimethyluric acid was not significantly affected by extended cold preservation periods in either UW or SLS solutions. Similarly, the amount of residual theophylline remained stable in all groups, suggesting that alternative metabolic routes were not modified. These studies show that cold preservation in SLS solution is as effective as that in UW solution in terms of cell viability, cytochrome P-450 content, and activity toward theophylline. In addition, the significant reduction in cytochrome P-450 in conjunction with unaffected theophylline disposition suggests that certain cytochrome P-450 isoforms are specifically damaged by cold preservation and rewarming.

Adenosine↗

PubMed2001

Proton magnetic resonance spectroscopy of Sjögren-Larsson syndrome heterozygotes.

A deficit of fatty alcohol:NAD+ oxidoreductase complex (FAO) activity has been detected in patients with the Sjögren-Larsson syndrome (SLS). A moderate decrease in FAO activity has also been reported in heterozygote SLS subjects. Abnormal peaks were detected with proton magnetic resonance spectroscopy (1H-MRS) in homozygote SLS subjects. The purpose of this study was to examine whether 1H-MRS can be used to detect metabolic and/or pathological abnormalities in heterozygote SLS subjects. Four SLS heterozygotes were examined using 1H-MRS. A moderate decrease in FAO activity was demonstrated in two of the four heterozygotes. Abnormal peaks were detected at 0.9 ppm in the spectrum from cerebral hemispheres of every heterozygote. 1H-MRS was able to detect an abnormal accumulation of fatty alcohols and lipids, which is expected to increase due to an decrease in FAO activity or dysmyelination in heterozygote SLS subjects. Thus, 1H-MRS is suggested to be a powerful tool in the screening of SLS heterozygotes.

Adult↗

PubMed1997

Insertional inactivation of streptolysin S expression is associated with altered riboflavin metabolism in Streptococcus pyogenes.

Transposon Tn916 mutagenesis was used to create a mutant of Streptococcus pyogenes M type 3, designated ISS417, in which the ability to produce streptolysin S (SLS) and several other exoproteins was impaired. Concomitantly, the mutant became dependent upon riboflavin for growth and was able to grow in Todd Hewitt broth (THB) when supplemented with riboflavin or riboflavinrich yeast extract. The parent strain was apparently able to utilize THB-derived components as a substitute for riboflavin, while the mutant was not. Although the parent strain grew well in synthetic medium, it was unable to produce SLS, except when it was supplemented with a small amount of THB. Thus, a component of THB was able to "trigger" SLS formation in the parent strain. The mutant grew well in this medium, but was unable to produce SLS even when it was supplemented with THB. Southern hybridization analysis revealed that the ISS417 mutant harbours a single transposon insertion in its chromosome. Phage transduction experiments showed that the riboflavin dependency and the inability to make SLS phenotypes are co-transducible. The pleotrophic properties of the ISS417 mutant differ from those reported for insertional inactivation of the mga locus which regulates production of a number of surface proteins in S. pyogenes and the sar locus which regulates production of a number of exoproteins in Staphylococcus aureus. In view of the possibility that there exist a genetic linkage between the riboflavin biosynthetic pathway and expression of the oxygen-stable SLS, we hypothesize that SLS has a role in the growth economy of S. pyogenes.

Bacterial Proteins↗

PubMed1990

Stem-loop structures at the 3' end of tobacco Rubisco large subunit mRNA.

There are two inverted repeat nucleotide (nt) sequences, each capable of forming a stem-loop structure (sls) at the 3' end of the tobacco Rubisco large subunit mRNA (rbcL). The smaller sls is followed by a larger sls. The in vivo functions of the 3' sls of the rbcL mRNA were characterized using the Escherichia coli system. S 1 mapping of the rbcL transcripts synthesized in E. coli revealed that the 3' end of a major transcript in the bacterial cell is almost identical to the 3' end of authentic chloroplast (cp) rbcL mRNA. This native 3' end is located 4 nt downstream from the larger sls for the cp mRNA and 6 nt for the bacterial transcript, respectively. Deletion experiments show that the larger sls is essential for producing the native 3' end of rbcL mRNA in E. coli. The sls do not function as an efficient transcription terminator but can stabilize upstream mRNA segments in vivo.

Base Sequence↗

PubMed2004

Expression and evolution of delta9 and delta11 desaturase genes in the moth Spodoptera littoralis.

Desaturation of fatty acids is a key reaction in the biosynthesis of moth sex pheromones. The main component of Spodoptera littoralis sex pheromone blend is produced by the action of Delta11 and Delta9 desaturases. In this article, we report on the cloning of four desaturase-like genes in this species: one from the fat body (Sls-FL1) and three (Sls-FL2, Sls-FL3 and Sls-FL4) from the pheromone gland. By means of a computational/phylogenetic method, as well as functional assays, the desaturase gene products have been characterized. The fat body gene expressed a Delta9 desaturase that produced (Z)-9-hexadecenoic and (Z)-9-octadecenoic acids in a (1:4.5) ratio, whereas the pheromone gland Sls-FL2 expressed a Delta9 desaturase that produced (Z)-9-hexadecenoic and (Z)-9-octadecenoic acids in a (1.5:1) ratio. Although both Delta9 desaturases produced (Z)-9-tetradecenoic acid from myristic acid, transformed yeast grown in the presence of a mixture of myristic and (E)-11-tetradecenoic acids produced (Z,E)-9,11-tetradecadienoic acid, but not (Z)-9-tetradecenoic acid. The Sls-FL3 gene expressed a protein that produced a mixture of (E)-11-tetradecenoic, (Z)-11-tetradecenoic, (Z)-11-hexadecenoic and (Z)-11-octadecenoic acids in a 5:4:60:31 ratio. Despite having all the characteristics of a desaturase gene, no function could be found for Sls-FL4.

Amino Acid Sequence↗

PubMed2005

Variations in the mRNA expression of inflammatory mediators, markers of differentiation and lipid-metabolizing enzymes caused by sodium lauryl sulphate in cultured human keratinocytes.

Detergents are well known irritants. Effects of the detergent sodium lauryl sulphate (SLS) on cell toxicity using the XTT assay and mRNA expression of inflammatory mediators, markers of keratinocyte differentiation and enzymes synthesizing barrier lipids using real-time PCR were studied in cultured differentiated keratinocytes. After exposure for 24 h to SLS concentrations at 0.002% or above, toxic effects were observed. When a lower SLS concentration (0.00075%) was used the mRNA expression of inflammatory mediators peaked around 4-8 h. The expression of enzymes involved in the synthesis of cholesterol, fatty acids and ceramides and markers of keratinocyte differentiation also increased but after 24 h. In cells exposed to 0.000125-0.0015% SLS, a concentration-dependent induction of the expression of inflammatory mediators was found after 4 h. Similar changes were found after 24 h for involucrin and enzymes involved in ceramide synthesis. The mRNA expression of HMG-CoA synthase and reductase, long-chain acyl-CoA synthase and transglutaminase also peaked after 24 h, but maximal induction was observed already at 0.00075% SLS. In conclusion, SLS induces an inflammatory response in keratinocytes and alters the mRNA expression of important barrier lipid enzymes and markers of keratinocyte differentiation, of possible importance for the irritant properties of SLS.

Cell Differentiation↗

PubMed1998

Characterization of cytotoxicity induced by sphingolipids in multidrug-resistant leukemia cells.

Certain sphingolipids (SLs) exert fundamental roles in differentiative, growth-inhibitory and apoptotic pathways induced by a number of agents in leukemia cells. Multidrug-resistance (MDR) is a major cause of therapeutic failure in leukemia. SLs are among the diverse substrates for the MDR p-170 glycoprotein drug-efflux pump. We tested the hypothesis that expression of MDR would thereby block the cytotoxicity induced by the SLs sphingosine, sphinganine and N-hexanoyl-sphingosine. An MDR-expressing subline of murine P388 leukemia cells demonstrated an ED50 value > or = 2 log10 higher than the parental line in response to doxorubicin. In contrast, the ED50 values for each of the SLs were only approximately 1.5 to two-fold higher in the MDR line than in the parental; induction of DNA damage by SLs was comparable or actually greater in MDR compared to parental cells. Therefore, expression of MDR does not significantly affect the cytotoxic function of these SLs, nor do these SLs likely contribute to MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗