[Fatal erythroderma in a young Moroccan]. / Erythrodermie fatale chez un jeune marocain.

The purpose of this report is to describe a case involving a young Moroccan who abruptly developed pruritic papulo-vesicular lesions with erythroderma. Secondary development of jaundice and tumoral syndrome lead to diagnosis of an acute form of adult T-cell leukemia/lymphoma associated with HTLV-1 infection. The patient died within three months. To o ur knowledge, this is the first such case reported in Morocco.

Molecular detection and genotyping of human papillomavirus in cervical carcinoma biopsies in an area of high incidence of cancer from Moroccan women.

Cervical cancer is a leading cause of cancer-related deaths in developing countries, and the human papillomavirus (HPV) is linked etiologically to cervical cancer. Eighty nine cervical carcinoma biopsies collected from women visiting the Oncologic Center in Casablanca (Centre Hospitalier Universitaire Ibn Rochd, Morocco) for cervical cancer symptoms, were screened for HPV DNA by polymerase chain reaction amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 45, and 59. Using very high stringency hybridization the HPV types could be easily distinguished. After preliminary clinical sorting, 92% (82/89) of the samples were found to be HPV-positive. Among the samples infected by a single HPV, type 16 was the most frequent 36.6% (30/82) of the positive samples, followed by HPV 18; 19.5% (16/82). Double or even multiple infections by the different HPV types were also detected (35.5% of the positive samples); dual infections were the more frequent, with the following combinations of HPVs: HPV16/HPV18 (21% of the positives samples) and HPV16/HPV45 (8.5%).

Role of glucagon in the control of heat production in ducklings.

Glucagon is known to be a central modulator of neural activity and a peripheral thermogenic effect. The purpose of this study was to better understand the role of glucagon in the control of heat production, shivering and particularly as a mediator of nonshivering thermogenesis (NST) in ducklings. In order to study the mechanism of NST, an intracerebroventricular (i.c.v.) injection of glucagon (10(-7) M) in to thermoneutral (TN), chronically glucagon treated (GT) and cold acclimatized (CA) ducklings exposed to acute cold (4 degrees C) or a thermoneutrality (25 degrees C), was performed. At 25 degrees C ambient temperature (Ta), the metabolic rate (MR) remained unchanged after glucagon injection. At 4 degrees C Ta i.c.v. glucagon injection, no significant change in MR was observed in GT and CA ducklings during 160 min of cold exposure, whereas there was 63% decrease in MR in (TN) ducklings (5.02 +/- 0.1 2 vs 7.91 +/- 0.1 4 W/kg(-1) p < 0.05). Shivering activity was completely suppressed in TN and GT ducklings after glucagon administration. The NST was estimated to be 3.26 W/kg. This findings suggest that glucagon administered into the brain has no thermogenic effect but could be involved in the central control of somatic motricity, and here we demonstrated for the first time, of our knowledge, that central glucagon have a role in the development of nonshivering thermogenesis during prolonged cold via an inhibition of shivering in birds.

Sleep during Ramadan intermittent fasting.

During the month of Ramadan intermittent fasting, Muslims eat exclusively between sunset and sunrise, which may affect nocturnal sleep. The effects of Ramadan on sleep and rectal temperature (Tre) were examined in eight healthy young male subjects who reported at the laboratory on four occasions: (i) baseline 15 days before Ramadan (BL); (ii) on the eleventh day of Ramadan (beginning of Ramadan, BR); (iii) on the twenty-fifth day of Ramadan (end of Ramadan, ER); and (iv) 2 weeks after Ramadan (AR). Although each session was preceded by an adaptation night, data from the first night were discarded. Polysomnography was taken on ambulatory 8-channel Oxford Medilog MR-9000 II recorders. Standard electroencephalogram (EEG), electro-oculogram (EOG) and electromyogram (EMG) recordings were scored visually with the PhiTools ERA. The main finding of the study was that during Ramadan sleep latency is increased and sleep architecture modified. Sleep period time and total sleep time decreased in BR and ER. The proportion of non-rapid eye movement (NREM) sleep increased during Ramadan and its structure changed, with an increase in stage 2 proportion and a decrease in slow wave sleep (SWS) duration. Rapid eye movement (REM) sleep duration and proportion decreased during Ramadan. These changes in sleep parameters were associated with a delay in the occurrence of the acrophase of Tre and an increase in nocturnal Tre during Ramadan. However, the 24-h mean value (mesor) of Tre did not vary. The nocturnal elevation of Tre was related to a 2-3-h delay in the acrophase of the circadian rhythm. The amplitude of the circadian rhythm of Tre was decreased during Ramadan. The effects of Ramadan fasting on nocturnal sleep, with an increase in sleep latency and a decrease in SWS and REM sleep, and changes in Tre, were attributed to the inversion of drinking and meal schedule, rather than to an altered energy intake which was preserved in this study.

Nitric oxide relaxes the vascular smooth muscle independently of endothelin-1- and U46619-induced intracellular increase of calcium.

A balance between circulating and locally released vasoconstrictors, such as endothelin-1 (ET-1), and vasodilators, such as nitric oxide, controls vascular smooth muscle tone. In the study reported here, using the technique of simultaneous measurements of intracellular free calcium ([Ca2+]i) and tension, we investigated the effects of a nitric oxide donor, sodium nitroprusside (NaNP) on endothelin-1- and U46619- [a thromboxane angiotensin-II (TXA-II) mimetic] induced sustained increases in tension and [Ca2+]i in intact and endothelium-denuded rabbit thoracic aortas. Our results showed that, in both intact and endothelium-denuded preparations, the nitric oxide donor NaNP (10(-6) M) reverses the ET-1- (10(-7) M) and U46619- (10(-7) M) induced sustained increase in tension but not in [Ca2+]i. However, it did not reduce the ET-1- and U46619-induced responses. Our data suggest that nitric oxide production modulates vascular smooth muscle tension via a mechanism that is independent of that generated by vasoconstrictors such as ET-1 and TXA-II.

Bronchial responsiveness among inbred mouse strains. Role of airway smooth-muscle shortening velocity.

To investigate the relationship between bronchial responsiveness and airway smooth-muscle (ASM) contractile properties, we studied inbred mice with known interstrain differences in airway responsiveness. Using oscillatory mechanics, we confirmed that A/J mice were hyperresponsive to methacholine (MCh) as compared with mice of the C3H/HeJ and C57BL/6J strains. Analysis of respiratory system resistance and elastance at different flow oscillation frequencies indicated that interstrain differences in responsiveness are present in both central and peripheral airways of these mice. We used video microscopy to measure the rate of contraction of explanted airways, and found that the airways of A/J mice contracted more rapidly than those of C3H/HeJ or C57BL/6J mice. In studies of a fourth strain (Balb/C) of mice, we found both bronchial hyperresponsiveness and increased ASM shortening velocity. The rank order of responsiveness among strains was the same as that for shortening velocity (A/J > Balb/C > C3H/HeJ > C57BL/6J). Furthermore, in each strain of mice, shortening velocity correlated with the achieved degree of airway narrowing and with a greater likelihood of airway closure in individual airways. In contrast, generation of isometric tension in trachealis, morphometric measurements of tracheal ASM, tracheal myosin content, and dose-response curves for MCh of explanted intraparenchymal bronchi failed to correspond to the in vivo phenotype of airway reactivity. These results indicate that bronchial responsiveness is related to ASM shortening velocity, and underscore the importance of smooth-muscle dynamics in understanding the mechanisms of bronchial responsiveness.

Epidemiological study: chronotype and daytime sleepiness before and during Ramadan.

Few epidemiological data have been reported on the relation between Ramadan fasting, life habits (meal frequency, sleep habits) and daytime sleepiness during Ramadan. This paper presents the results of a detailed study of the chronotype and daytime sleepiness before and during Ramadan. It was conducted on a sample of 264 subjects aged between 20 and 30 years. Results have revealed a significant decrease in the meal frequency during Ramadan compared with the control period. Before Ramadan, the majority of subjects woke up between 6 and 7 a.m. and went to sleep between 10 and 11 p.m. however, during Ramadan fasting, they woke up after 8 a.m. and preferred to go to sleep later (after midnight). Chronotype as evaluated by the Horne and Ostberg scale was changed significantly during Ramadan: an increase of the evening type and a decrease in the morning type of subjects was observed. Daytime sleepiness as evaluated by the Epworth Sleepiness Scale was significantly increased.

Effect of neuropeptide Y on bradykinin-induced release of prostacyclin and thromboxane from guinea pig perfused lung.

We have previously reported that neuropeptide Y (NPY) inhibits responses induced by various agonists (noradrenaline, vasoactive intestinal peptide, substance P,5-hydroxytryptamine) in isolated guinea pig trachea. Although the underlying mechanisms have not been fully characterized, it was found that the NPY-evoked inhibition was specifically expressed with agents for which locally released prostaglandins (PGs) are important determinants for their myotropic activity. In the present study, we have extended these findings by examining whether NPY was capable of regulating the release of prostacyclin and thromboxane A2 induced by bradykinin (BK) from naive and ovalbumin-sensitized guinea pig perfused lungs. Our results showed that infusion of NPY (0.24 microM) through the lung significantly inhibited the release of 6-keto-PGF1 alpha (> 30%) and thromboxane B2 (50%) induced by intraarterial administration of BK (3 micrograms) from untreated and ovalbumin-sensitized guinea pig perfused lung. However, the inhibitory effect of NPY was lost in the immunological production of prostaglandins. These results suggest that NPY may act as a regulatory agent of the release of cyclooxygenase-derived products by possibly acting on events preceding phospholipase A2 activation.

Modulation of Ca2+ and Na+ transport by taurine in heart and vascular smooth muscle.

Using the whole-cell voltage clamp technique, taurine was found to affect different types of various ionic currents including T and L-type Ca2+ currents, slow Na+ and fast Na+ currents as well as the delayed outward K+ current. Also, in normal situations, taurine had no effect on the Na(+)-Ca2+ exchange current. The effect of taurine on the different types of ionic currents appears to depend on [Ca2+]o and [Ca2+]i and may also vary according to the tissue or cell type studied. Using standard Ca2+ imaging techniques, short-term exposure (10 to 20 min) of single heart cells and aortic vascular smooth muscle cells was found to increase total intracellular free Ca2+ in a dose-dependent manner. However, using 3-dimensional Ca2+ and Na+ imaging techniques, long-term exposure of heart and vascular smooth muscle cells to taurine was found to decrease both nuclear and cytosolic Ca2+ without significantly changing either nuclear or cytosolic Na+ levels. Long-term exposure to taurine was found to prevent cytosolic and nuclear increases of Ca2+ induced by permanent depolarization of heart cells with high [K+]o. This preventive effect of taurine on nuclear Ca2+ overload was associated with an increase of both cytosolic and nuclear free Na+. Thus, the effect of long-term exposure to taurine on intranuclear Ca2+ overload in heart cells seems to be mediated via stimulation of sarcolemma and nuclear Ca2+ outflow through the Na(+)-Ca2+ exchanger.

Specific cyclic nucleotide phosphodiesterase inhibitors differently modulate contractile kinetics in airway smooth muscle.

The involvement of various phosphodiesterases (PDEs) in controlling the time-dependent mechanical properties of guinea pig trachealis smooth muscles was determined by using different classes of PDE inhibitors as pharmacological tools. These drugs produced low amplitude and long-lasting dose-dependent relaxations on the resting tone with the following EC50 values: rolipram, 3 nM; indolidan, 0.11 microM; and zaprinast, 0.5 nM and 1 microM. These PDE inhibitors were 50% less active than 1 microM norepinephrine. The effects of the drugs were also tested on carbachol-induced contractions and norepinephrine-evoked relaxations. Zaprinast, but not rolipram nor indolidan, decreased the rate of rise of contraction, thus prolonging the time to reach the plateau by 75% without modifying the magnitude of the responses. Zaprinast and rolipram significantly increased the total length of the norepinephrine effect by 25 and 35%, respectively. Similar results were obtained in a dose-dependent manner on isoproterenol-induced relaxations. In contrast, a higher concentration of indolidan was required to affect the amplitude, duration, and time to peak of isoproterenol- or norepinephrine-induced relaxations. These results indicate that PDE IV (rolipram sensitive) and PDE I, and less likely PDE V (both zaprinast sensitive), are involved in the control of guinea pig airway contractile kinetics, whereas PDE III (indolidan sensitive) is essentially involved in the modulation of the resting tone. Four cytosolic isozymes were identified in bovine airway smooth muscles (ASMs); PDE I (calmodulin-dependent PDE), PDE II (cGMP-stimulated PDE), PDE IV (cAMP-specific and rolipram-sensitive PDE), and PDE V (cGMP-specific and zaprinast-sensitive PDE). Characterization of PDE isoforms present in the microsomal fraction by HPLC showed the presence of PDE IV, PDE V, and to a lesser extent PDE III. However, PDE III was not detected in ASM cytosol. Using newly synthesized radioligands, binding studies confirmed the low level of expression of PDE III and the presence of PDE IV. We conclude that PDE I controls the rate of contraction, whereas PDE V and PDE IV prolong the time of relaxation induced by NE. PDE V would control the ASM responsiveness by regulating the intracellular cGMP concentration, which in turn would both activate PKG and stimulate PDE II (cGS-PDE). Since the various isozymes of PDE are differently involved in the kinetic control of the mechanical events in ASM, they represent physiologically relevant and important pharmacological targets.

Effects of interleukin-1 alpha on DNA repair in human ovarian carcinoma (NIH:OVCAR-3) cells: implications in the mechanism of sensitization of cis-diamminedichloroplatinum(II).

The cytokine interleukin-1 alpha (IL-1 alpha) showed a cytostatic effect on human ovarian carcinoma cells and significantly enhanced the antiproliferative activity of cis-diamminedichloroplatinum(II) (cisplatin) toward the NIH:OVCAR-3 tumor cell line in culture. The factor of sensitization was 15-20-fold. The maximum levels of sensitization were observed both with simultaneous exposure to cisplatin and IL-1 alpha and with 24-hr pretreatment with IL-1 alpha. Synergy between these agents was diminished when cells were pretreated with an IL-1 alpha-specific receptor antagonist, indicating that synergistic interaction was receptor mediated. Using atomic absorption spectroscopy, we evaluated the cellular accumulation of cisplatin and the DNA platination; the results showed that IL-1 alpha increased cellular accumulation of cisplatin and DNA platination. Cisplatin did not affect IL-1 alpha accumulation in NIH:OVCAR-3 cells. Further studies showed that IL-1 alpha reduced the removal of platinum from DNA. These results strongly suggest that IL-1 alpha inhibits DNA repair, and this decrease in DNA repair may explain, in part, the strong synergistic interaction between IL-1 alpha and cisplatin in NIH:OVCAR-3 cells.

R-type calcium channel involved in endothelin-1-induced contraction of rabbit aorta.

The mechanism of Ca2+ mobilization induced by endothelin-1 (ET-1) and the receptor subtype responsible for this effect were examined in the rabbit aorta. We have used preparations with intact and denuded endothelium. Experiments were designed to measure both Fura-2-[Ca]i fluorescence and contractile tension simultaneously. In both preparations, ET-1 (10(-10) to 10(-7) M) induced contractions and increases of the fluorescence ratio in a concentration-dependent manner. ET-1-induced contractions and elevations of [Ca]i were blocked by the dual L- and R-type calcium-channel blocker (-)PN200 110 (10(-6) M), whereas nifedipine (10(-6) M) affected only the latter parameter. BQ-123, a selective ET(A) receptor antagonist, almost totally blocked the ET-1-induced contraction and elevation of [Ca]i. Our results illustrate the activation of the R-type calcium channel by ET-1 on the smooth muscle and on the endothelium rabbit aorta. This effect of ET-1 on the R-type calcium channel is mediated by ET(A) and ETB receptor stimulation.

Mechanisms of resistance to ansamycin antibiotics in human breast cancer cell lines.

We recently reported that multidrug-resistant, P-170 glycoprotein-positive, Adriamycin-selected, human breast tumor (MCF7/ADRR) cells were resistant to the benzoquinonoid ansamycin antibiotics geldanamycin (GL) and herbimycin A (HA) and that significantly fewer hydroxyl radicals were formed in resistant cells. We have carried out additional studies to define the mechanisms of cytotoxicity of and resistance to GL and HA, by directly examining the interactions of these drugs with P-170 glycoprotein using photoaffinity labeling. We found that both GL and HA inhibited binding of azidopine to P-170 glycoprotein in a dose-dependent manner. We have developed a 10-fold GL-resistant cell line (MCF7/GLR) by continuous drug exposure. Our studies indicated no significant differences in free radical formation between wild-type MCF7 cells and MCF7/GLR cells. Uptake and efflux studies indicated a small decrease in the GL accumulation but no difference in the efflux of GL in these cells. Verapamil had no effect on cellular accumulation of GL in wild-type MCF7 cells or MCF7/GLR cells. Verapamil significantly increased the accumulation of GL in MCF7/ADRR cells and enhanced GL cytotoxicity 12-fold, suggesting that GL interacted with the P-170 glycoprotein. Using reverse transcription-polymerase chain reaction, we found no expression of the mdr1 gene; however, expression of the multidrug resistance-associated protein was about 2-fold higher in MCF7/GLR cells. Taken together, these studies indicate that the mechanisms of GL resistance are multifactorial. Although decreased free radical formation may not play a significant role in low levels of GL resistance, e.g., in MCF7/GLR cells, both overexpression of mdr1 and decreased free radical formation contribute to GL resistance in highly resistant cells such as MCF7/ADRR cells.

Potentiation of antitumor activities of carboplatin and camptothecin by interleukin-1 alpha against human ovarian carcinoma in vivo.

Interleukin-1 alpha significantly potentiated the cytotoxicity of carboplatin (8-fold) and camptothecin (4-fold) during simultaneous drug exposure in human ovarian NIH: OVCAR-3 cancer cells in vitro. Treatment of human ovarian tumor cells grown as xenografts in nude mice with IL-1 alpha followed by either carboplatin or CTP-11 at minimally toxic doses significantly (2-3-fold and 7-fold for carboplatin and CTP-11, respectively) enhanced antitumor activity of either agent alone, indicating that IL-1-alpha-drug combinations may be potentially more effective for the treatment of ovarian tumors, including those difficult to cure in the clinic.

Inhibition of DNA repair and sensitization of cisplatin in human ovarian carcinoma cells by interleukin-1 alpha.

Interleukin-1 alpha induced an increase in both the cellular accumulation of cis-diamminedichloroplatinum (II) (cisplatin) and DNA platination and significantly reduced the removal of platinum from DNA of human ovarian (NIH: OVCAR-3) carcinoma cells in culture. The combinations of IL-1 alpha and cisplatin were highly synergistic against these ovarian carcinoma cells and maximum levels of sensitization (15-20-fold) were observed during simultaneous exposure of cisplatin and IL-1 alpha. IL-1 alpha specific receptor antagonist decreased this synergy. These results strongly indicate that IL-1 alpha inhibits DNA repair, and this inhibition of DNA repair may explain, in part, a strong synergistic interaction between IL-1 alpha and cisplatin in NIH: OVCAR-3 cells.

Antagonism of the inhibitory action of neuropeptide Y (NPY) in guinea-pig trachea by the C-terminal fragment NPY (2-36).

The C-terminal fragment of neuropeptide Y (NPY), NPY(2-36) was used as a means of discriminating between two differently located NPY receptor sites in guinea-pig trachea. Both NPY and NPY(2-36) reduced the maximal relaxation elicited by vasoactive intestinal peptide (VIP). In contrast, the C-terminal fragment did not mimic the inhibitory action of NPY on the noradrenaline-(NA) evoked response. However, pretreatment of the trachea with 30 nM NPY(2-36), 5 min before generating NA and VIP concentration-response curves in the presence of NPY, abolished the inhibitory effect of NPY on NA-elicited response but did not affect the modulatory action of NPY on VIP-induced relaxation. These results suggest that the two differently located NPY receptor sites in guinea-pig trachea are of two distinct subpopulations.

The rabbit saphenous vein: a tissue preparation specifically enriched in NPY-Y1 receptor subtype.

Neuropeptide Y (NPY), a co-transmitter in noradrenergic sympathetic nerves of the cardiovascular system, was tested on isolated segments of rabbit saphenous vein. NPY caused strong, long lasting and concentration dependent contraction resistant to adrenergic blockade. PYY, a NPY related peptide, shared this property. As pressor agents, both peptides were about 100-fold more potent than norepinephrine and at their highest concentrations caused a contraction of a similar magnitude as NE. Gradual shortening of N-terminal end of the NPY molecule caused major loss of potency and reduction of intrinsic activity; which suggests that the entire molecule is required to produce full biological activity in this vascular preparation. Addition of [Leu31,Pro34]pNPY, a NPY analog with specific agonist properties at Y1 receptors, mimicked the effect of NPY whereas NPY (13-36), a selective agonist at Y2 receptors, caused a 2 log unit shift to the right of the concentration response curve. These results suggest that the vasoconstrictor effect of NPY in rabbit saphenous vein results from a direct effect on smooth muscle cells and that the receptors involved are of the Y1 subtype.

Evaluation of truncated neuropeptide Y analogues with modifications of the tyrosine residue in position 1 on Y1, Y2 and Y3 receptor sub-types.

Substitutions of the tyrosine residue in position 1 of truncated neuropeptide Y (N-terminal fragment 1-4 linked to C-terminal fragment 18-36 by the epsilon-aminocaproic acid) produced analogues that compete for specific [125I]polypeptide YY (PYY) binding in the frontoparietal cortex (Y1-enriched) with a profile best fitted to a two site-model with KD values in the low and high nM range, respectively. In the hippocampal membrane preparations (Y2-enriched), halogen substitutions on the aromatic ring generated analogues with competition profiles best fitted to a one-site model, revealing differences between the two binding assays and the interaction of these analogues with the Y1 and Y2 receptor sub-types. In the rat vas deferens (Y2-enriched), all truncated analogues inhibited the twitch response with similar or slightly weaker potency than the native molecule. In contrast, these molecules were markedly less potent than neuropeptide Y (NPY) in the rabbit saphenous vein (Y1-enriched) and the rat distal colon (Y3-enriched). Some of the truncated analogues were inactive at up to microM concentrations in the rat distal colon, demonstrating the distinct structural requirement of the receptor sub-type present in this bioassay. These results revealed that amino acid residues between positions 5 and 17 are critical for the maintenance of optimal affinity for the NPY receptors present in the rabbit saphenous vein and the rat distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Doxorubicin-induced oxygen free radical formation in sensitive and doxorubicin-resistant variants of rat glioblastoma cell lines [corrected and republished erratum originally printed in FEBS Lett 1993 May 17;322(3):295-8].

We have studied the formation of hydroxyl radical (OH.) induced by doxorubicin in a series of doxorubicin- or vincristine-selected variants of C6 rat glioblastoma cells in culture by electron-spin resonance spectroscopy using 5,5'-dimethyl-1-pyrroline-1-oxide as a spin trap. Wild-type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration-dependent OH. formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450-reductase. In highly doxorubicin-resistant cells, OH. formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug-resistant phenotype, OH. formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH. formation were obtained. Protection against OH. formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells.

Doxorubicin-induced lipid peroxidation and glutathione peroxidase activity in tumor cell lines selected for resistance to doxorubicin.

Doxorubicin-induced lipid peroxidation was evaluated in four human or murine cell strains in culture and in their doxorubicin-resistant variants, by the quantification of malondialdehyde produced after a 2-h incubation of cells with the drug. Significantly increased malondialdehyde levels were obtained 24 h after doxorubicin treatment in three of the wild-type cell lines with doses as low as 0.05-0.1 micrograms/ml, which is within an order of magnitude of the concentration of the drug which inhibits cell growth by 50%. This production of malondialdehyde was abolished in two doxorubicin-resistant strains, even with high doses of drug (100-300 micrograms/ml), but was maintained in the third resistant line. No malondialdehyde production was observed in the fourth cell line, sensitive or resistant. It is remarkable that an enhancement of selenium-dependent and non-selenium-dependent glutathione peroxidase activities was exhibited during the acquisition of resistance to doxorubicin in the two first lines, but not in the third, whereas a constitutively high non-selenium-dependent glutathione peroxidase activity existed in the doxorubicin-sensitive and doxorubicin-resistant variants of the fourth cell line. Gene expression of selenium-dependent glutathione peroxidase and of glutathione S-transferase pi, which is known partially to bear a non-selenium-dependent glutathione peroxidase activity, were correlated with the corresponding enzyme activities. It appears, therefore, that the already known enhancement of glutathione peroxidase activity and expression in doxorubicin-resistant cell lines has a quantifiable consequence upon doxorubicin-induced lipid peroxidation and may have consequences in the mechanism of resistance to this drug.