Effect Of Prior Treatment Research Articles

Everolimus in patients with metastatic renal cell carcinoma refractory to VEGF-targeted therapy: REACT subgroup analysis of prior therapy.

391 Background: Efficacy of everolimus (EVE) in metastatic renal cell carcinoma (mRCC) refractory to vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy is well established. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to provide patients with VEGFR-TKI-refractory mRCC access to EVE in advance of regulatory approval. Methods: REACT, an open-label, international, expanded-access clinical trial (Clinicaltrials.gov: NCT00655252 ) enrolled patients with measurable or nonmeasurable mRCC of any histology who were intolerant of, or progressed while on, VEGFR-TKI therapy. Long-term safety of EVE 10 mg/day in patients with mRCC, as determined by overall incidence of grade 3/4 and serious adverse events (AEs) was documented. RECIST-defined tumor response was also assessed by local investigator. Subgroup analyses evaluated effect of prior treatment on safety and efficacy of EVE. Results: Of 1367 patients enrolled, most (92.7%) had progressed on prior VEGFR-TKI therapy, and some (24.4%) were VEGFR-TKI intolerant. Across patient subgroups by prior VEGFR-TKI treatment, median EVE treatment duration was similar (Table). Best overall response rates were similar in the VEGFR-TKI-intolerant subgroup and overall populations: respectively, 1.8% and 1.7% had partial response (PR) while 53.5% and 51.6% had stable disease (SD). Incidence of grade 3/4 AEs across all prior treatment subgroups were similar to those of the overall population. (See table.) Conclusions: Patients enrolled in REACT derived benefit from EVE irrespective of prior VEGFR-TKI therapy, including VEGFR-TKI-intolerant patients. EVE is well tolerated and affords disease stabilization in the majority of patients with VEGFR-TKI-refractory mRCC, and is the standard of care in this patient population. [Table: see text]

Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats

In addition to producing analgesia, opioids can increase sensitivity to pain (opioid-induced hyperalgesia [OIH]) in humans and rodents. Tolerance/OIH is likely mediated by similar mechanisms that lead to development of hyperalgesia after nerve injury (neuropathic pain). OIH may be a reason for loss of opioid efficacy and/or a worsening of pain. Ultra-low-dose (ULD) opioid evokes hyperalgesia independently of analgesia. Tolerance to ULD-OIH develops with repeated dosing in rats. The effects of ULD opioids were characterized in two distinct situations where hyperalgesia is expected to occur: following acute opioid treatment and after nerve injury. First, ULD morphine was repeatedly administered (2x day for 5 days) by intrathecal (i.t., 0.01 microg) or intraperitoneal (i.p., 20 microg/kg) routes in rats. Second, morphine (0.01 microg i.t.; 20 microg/kg i.p.) was administered (2x day for 5 days) prior to acute morphine (30 microg i.t.; 10 mg/kg i.p). Third, ULD morphine (20 microg/kg/2x day, i.p.) was given either immediately after nerve injury (days 1-28) or when hyperalgesia was manifested (days 7-14). The tail-flick and paw-pressure tests were used in noninjured and nerve-injured rats, respectively. Tolerance was developed to OIH with repeated ULD morphine by the i.p. route but not the i.t. route. Prior exposure to ULD morphine (i.p.) caused prolongation of morphine analgesia in intact rats and inhibition of the development (but not reversal) of hyperalgesia in nerve-injured rats. Abolishment of OIH (pain desensitization) may diminish activation of pain facilitatory systems due to nerve injury and opioid treatment. Although the translational aspect of this preclinical study has limitations, the present data may suggest a new strategy for the pre-emptive use of ULD opioids to prevent the development of neuropathic pain with certain procedures or disease states.

Effect of corrosion medium on the nonuniformity of plastic microstrains in the microstructure of D16 aluminum alloy

The microstructure of alloy D19 is studied and the effect of prior treatment of the alloy in a corrosive medium on the parameters of nonuniformity of the fields of plastic strains under conditions of uniaxial tension is evaluated. Results of uniaxial tensile tests of flat specimens with a dividing grating with cell size commensurable with the characteristic grain size are used for determining the longitudinal and transverse microstrains, the principal microstrains, their intensity, and the parameters of the strained state of the grains. One- and two-point joint distributions and correlation functions of the components of microstrains in the microstructure of a sheet from aluminum alloy D16 are plotted experimentally. The probabilities of occurrence of local overloads in individual grains and their propagation to couples and triples of grains are determined.

Effect of prior treatment with resveratrol on density and structure of rat long bones under tail-suspension

Physical inactivity during space flight or prolonged bed rest causes rapid and marked loss of bone mass in humans. Resveratrol, a red wine polyphenol that is currently under study for its therapeutic antioxidant properties, has been shown to significantly modulate biomarkers of bone metabolism, i.e., to promote osteoblast differentiation and to prevent bone loss induced by estrogen deficiency. However, there is no direct evidence supporting its inhibitory effect toward bone loss during physical inactivity. In the present study, effects of resveratrol on bone mineral density (BMD), bone mineral content, and bone structure were examined in the femora and tibiae of tail-suspended and unsuspended rats using X-ray micro-computed tomography (micro-CT). Rats were treated with 400mg/kg/day of resveratrol for 45days and half of them were suspended during the last 2weeks of treatment. Suspension caused a decrease in tibial and femoral BMD and deterioration of trabecular and cortical bone. Bone deterioration during suspension was paralleled by increased bone marrow area, which could be caused by an increase in stromal cells with osteoclastogenic potential or in adipocytes. Resveratrol had a preventive effect against bone loss induced by hindlimb immobilization. In particular, trabecular bone in the proximal tibial metaphysis was totally preserved in rats treated with resveratrol before tail-suspension.

Role of 5-HT 1A receptors in fluoxetine-induced lordosis inhibition

The selective serotonin reuptake inhibitor (SSRI), fluoxetine (Prozac®), is an effective antidepressant that is also prescribed for other disorders (e.g. anorexia, bulimia, and premenstrual dysphoria) that are prevalent in females. However, fluoxetine also produces sexual side effects that may lead patients to discontinue treatment. The current studies were designed to evaluate several predictions arising from the hypothesis that serotonin 1A (5-HT 1A) receptors contribute to fluoxetine-induced sexual dysfunction. In rodent models, 5-HT 1A receptors are potent negative modulators of female rat sexual behavior. Three distinct experiments were designed to evaluate the contribution of 5-HT 1A receptors to the effects of fluoxetine. In the first experiment, the ability of the 5-HT 1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-2-pyridinylcyclohexanecarboxamide (WAY100635), to prevent fluoxetine-induced lordosis inhibition was examined. In the second experiment, the effects of prior treatment with fluoxetine on the lordosis inhibitory effect of the 5-HT 1A receptor agonist, (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT), were studied. In the third experiment, the ability of progesterone to reduce the acute response to fluoxetine was evaluated. WAY100635 attenuated the effect of fluoxetine; prior treatment with fluoxetine decreased 8-OH-DPAT's potency in reducing lordosis behavior; and progesterone shifted fluoxetine's dose–response curve to the right. These findings are consistent with the hypothesis that 5-HT 1A receptors contribute to fluoxetine-induced sexual side effects.

The effect of several cooking treatments on subsequent chilled storage of thawed deepwater pink shrimp (Parapenaeus longirostris) treated with different melanosis-inhibiting formulas

Abstract This work deals with the effect that different cooking methods have on quality of shrimps (Parapenaeus longirostris) during the chilled storage. Vacuum-cooking (sous-vide) and steaming were compared with the traditional cooking process in boiling water. The effect of prior treatment with several melanosis-inhibiting agents (with a commercial sulphite- or 4-hexylresorcinol-based formula) was also tested. Neither the melanosis-inhibiting blends nor the cooking methods used significantly affected the water-holding capacity, firmness or moisture content of the cooked shrimps. Spraying with a 4-hexylresorcinol-based formula was effective in preventing microbial growth during storage. Vacuum-cooking was also shown to be the most effective way of preventing microbial growth although the TVB-N content of cooked shrimps increased significantly. By discriminant analysis, a combination of prior spraying with 4-hexylresorcinol-based formula followed by vacuum-cooking, proved to be the best method for obtaining shrimps with a very good appearance and high microbial quality. The foregoing may be very important for the cooking industries.

Optimizing Rituximab in B-Cell Lymphoma

In this issue of the Journal of Clinical Oncology, three groups report their results with rituximab monotherapy in B-cell lymphoma. Following the approximately 50% response rate in recurrent or refractory indolent lymphoma reported in the pivotal trial, investigators have studied alternate dosing schedules in untreated and previously treated patients and have proposed both host and tumor characteristics that may predict the quality of response. How are the reports in the current issue of the Journal informative for current practice and clinical investigations? Witzig et al administered four weekly rituximab infusions to 36 previously untreated, follicular grade 1 lymphoma patients who, in their judgment, required no immediate therapy. Although the primary objective was to estimate the response rate, an important secondary end point was the time to initiating chemotherapy after rituximab treatment. The alternative of rituximab to the conservative approach of observation alone as initial management for selected patients may be considered advantageous if quality of life is improved or if the time to requiring chemotherapy is prolonged. The overall response rate in the North Central Cancer Treatment Group study was 72%, with a median time to progression of 2.2 years from registration—longer than previously reported in treatment-naive patients. The time to subsequent chemotherapy was, however, unexpectedly brief, at just 2.3 years after rituximab or approximately 2.4 years after registration. In two prior randomized phase III studies comparing observation to immediate therapy, time to initiating treatment was 2 and 2.4 years, respectively, after initial observation. In the study by Brice et al, the time to treatment failure was 3.6 years following 3 months of initial interferon alfa. Clearly, it can be hazardous to draw conclusions from a small patient sample, as reported by Witzig et al, in a disease as heterogeneous as follicular lymphoma. Perhaps these patients had more biologically aggressive disease than predicted at diagnosis, or perhaps the treating physicians had a lower threshold for administering chemotherapy, as the North Central Cancer Treatment Group did not establish standard criteria for initiating chemotherapy. It is also important to recall that the time to progression or time to initiating chemotherapy may be as much a function of the underlying biology of indolent lymphoma as the effect of prior treatment. Finally, the potential therapeutic benefit of rituximab was not maximized by the study design used by Witzig et al, which did not include re-treatment of responding patients. Previously, a 40% response rate was reported in follicular lymphoma patients with disease progression after initial response to rituximab and were subsequently re-treated weekly for 4 weeks. The goal, therefore, of rituximab monotherapy might then be best expressed as prolonging the time to requiring alternate therapy, allowing for rituximab re-treatment. Hainsworth et al studied this end point in a prospective trial in previously treated, but rituximab-naive, indolent B-cell lymphoma patients. The trial was a randomized phase II study, in which patients received four weekly rituximab infusions, with assessment of response at 6 weeks and random assignment of stable or responsive patients to maintenance rituximab delivered as four weekly treatments every 6 months, for a maximum of four courses or re-treatment (standard 4-week course) on disease progression. The purpose of this type of study is to evaluate various approaches so that the most promising can be selected for further study. Randomized phase II studies do not have adequate statistical power for definitive treatment comparisons, but seek to estimate treatment effect and toxicity in each arm, without patient selection bias. The primary study end point, duration of rituximab benefit as defined by the administration of alternative treatment, was not different between the two approaches in this trial. However, these results are only estimates, and imbalances in histology and the number of patients progressing before either maintenance or re-treatment may have influenced the results. In addition, rituximab benefit was based on a subjective end point—the requirement for alternate therapy—rather than an objective definition of response or duration of response. As in the Witzig et al JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 6 FEBRUARY 2

Epidemiology of erectile dysfunction and its risk factors: a practice-based study in Denmark.

The objective of this study was to estimate the prevalence of erectile dysfunction (ED) and its health-related correlates among Danish men, to evaluate the influence of age, tobacco smoking, educational level and medication and the needs for treatment and willingness to be treated. A validated questionnaire was sent to 4310 noninstitutionalized Danish men, aged 40-80 y. The men selected constituted all male patients aged 40-80 y in 12 general practitioner practices in a county of Zealand, representing both the urban and rural population. Besides age, education, marital status and International Index of Erectile Function, the questionnaire included the duration of sexual problems (ED, premature ejaculation, penile curvature), comorbidity, medication, risk factors and the effect of prior treatment and willingness to seek treatment for sexual problems. A total of 2210 men responded, giving a response rate of 51.3%. No difference in the response rate by age groups was noted. The prevalence of complete ED increased with increasing age: 40-45 y, ED: 4.5%; 50-55 y, ED: 11.1%; and 75-80 y ED: 52%. The frequency of ED increased three-fold from men without comedication to men having some kind of medical treatment. Risk factors included tobacco smoking and low educational level. Only 9% suffering from ED had received some kind of treatment. Of the treated men, 75% were satisfied with the treatment. Willingness to discuss sexual matters depended both upon the age of the man and his actual erectile function. Taboos were seen more frequently among elderly people. ED increases with age, but only 10% of the men with sexual problems seek advice. Medication predisposes to ED.

Elevated leptin levels in the peritoneal fluid of women with endometriosis

Objective: Leptin is a protein hormone produced by adipocytes in proportion to body fat stores that has also been shown to induce angiogenesis, regulate immune functions and increase in response to certain inflammatory cytokines. Endometriosis involves active angiogenesis around the implants and is characterized by elevated inflammatory cytokines in the peritoneal environment. For these reasons, we sought to assess the relationship, if any, between peritoneal fluid (PF) leptin levels and the presence of endometriosis. We evaluated the impact of the menstrual cycle, the stage and depth of endometriotic lesions and the effect of prior treatment with GnRH agonists (GnRH-a) on PF leptin levels.

Prior treatment history and its impact on criminal recidivism.

This study examines the hypothesis that treatment is a cumulative process; that is, treatment success is best viewed in terms of the patient's entire treatment history, rather than the index treatment episode. Three-hundred and eight patients with a primary heroin addiction were studied for 2 years posttreatment. Using posttreatment arrests as the dependent variable, the effects of prior treatment were assessed. Those with six or more prior treatment episodes and who had been in treatment for 12 or more months during the most recent episode averaged only 0.2 arrests in the 2 years posttreatment, while those with no prior treatment, but 12 or more months in the recent treatment averaged 0.88 arrests. Logistic analysis found that each prior treatment reduced the probability of a posttreatment arrest by 25%. Based on a linear regression, patients with six or more treatments prior treatments averaged half the number of posttreatment arrests as someone with no treatments before the index episode.

A single pretreatment with 8-OH-DPAT reduces behavioral indices of serotonin 1A receptor activation in ovariectomized rats

The effects of prior treatment with 8-OH-DPAT on 8-OH-DPAT-induced eating behavior, hypothermia, flat body posture and forepaw treading were examined in ovariectomized rats. Twenty-four hours after a single pretreatment with 0.25 mg/kg of the drug, the eating behavior and flat body posture induced by 8-OH-DPAT were reduced relative to that seen following the first treatment with the drug. In contrast, within 24 hr of the prior drug treatment, the drug's effects on forepaw treading and rectal temperature were unchanged. However, 7 days after prior treatment with 8-OH-DPAT, eating behavior, flat body posture and hypothermia induced by the drug were suppressed. Only forepaw treading remained unchanged. These findings are discussed in reference to similar studies of 5-HT 1A receptor agonist-induced modulation of behaviors in male rats.

Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival, and outcome.

Diffuse alveolar hemorrhage (DAH) complicating systemic lupus erythematosus (SLE) remains a devastating pulmonary complication of this systemic disease. We conducted this study to review the clinicopathologic presentation and the effects of prior treatment, presence of infection, and current treatment on the survival and outcome of patients with DAH and SLE. We reviewed the records of 15 SLE patients who experienced 19 episodes of DAH over a 10-year period in a single tertiary care hospital. These patients were compared with 57 previously reported cases. The 19 episodes of DAH represented 3.7% of the 510 admissions occasioned by various complications of SLE. As previously reported, the majority (66%) were women with a median age of 27 years. The onset was often abrupt: < 3 days in 12 of the episodes. In 3 patients (20%), DAH was the initial manifestation of SLE, compared with 11% in the literature series. In the other patients in the present series, DAH appeared a median of 31 months following the diagnosis of SLE, versus 35 months in the literature series. In only 42% of the episodes in the present series, compared with 66% in the literature series, was hemoptysis present at the time of admission. However, hemoptysis eventually appeared in all 19 episodes. Temperature elevation (> 38 degrees C) was another inconsistent finding, found in only 5 episodes (26%) in the present series. The most constant concurrent systemic finding was lupus nephritis (14/15 patients). This represents a significant increase when compared with the literature series (29/48 patients). In 8 of 10 patients in whom lung tissue was available, pulmonary capillaritis accompanied the DAH. This represents a marked difference in the underlying histologic pattern when compared with the literature series. In those patients, 72% (31/43 patients) had bland pulmonary hemorrhage, and capillaritis was described in only 6 patients. The overall patient mortality rate was 53% in the current series and 50% in the literature series. Factors associated with an increased mortality in the present series include the following: mechanical ventilation (62%) versus no mechanical ventilation (0%); infection (78%) versus no infection (20%); and cyclophosphamide therapy for the acute DAH episode (70%) versus no cyclophosphamide therapy (20%). The incidence of infection in DAH and SLE (9/19 episodes) is far greater than previously reported (7/ 57 episodes). One possible explanation for this difference is the increased use of outpatient immunosuppressive therapy with monthly intravenous cyclophosphamide therapy for lupus nephritis. Eighteen DAH episodes in the present series were treated with intravenous methylprednisolone. When one combines both the current and literature series experience (16 episodes), the use of plasmapheresis does not improve survival. Of the 7 patients in the present series who survived all episodes of DAH, 6 remain alive a median of 50 months post episode and without recurrence of DAH. Diffuse alveolar hemorrhage is an uncommon but lethal complication of SLE. The survival rate remains unchanged from previous reports. The absence of hemoptysis should not exclude this diagnosis, particularly in those patients who experience an acute pulmonary syndrome with new radiographic infiltrates accompanied by falling hematocrit and the presence of a hemorrhagic bronchoalveolar lavage. Evidence for lupus nephritis is present in the great majority of cases. Most cases demonstrate the histologic pattern of pulmonary capillaritis. The mortality is adversely affected by the need for mechanical ventilation, either the presence of infection at the time of admission or the development of infection in the hospital, and the use of cyclophosphamide for treatment of the acute event.

Naloxone blocks conditioned place preference induced by substance P and [pGlu 6]-SP(6–11)

The effect of prior treatment with the opioid receptor (opioceptor) antagonist naloxone on conditioned place preference produced by the neurotachykinin substance P (SP) and its C-terminal hexapeptide analog [pGlu 6]-SP(6–11) (SPC) was investigated in rats. Place conditioning was assessed using a circular open field partitioned into four quadrants that were equally preferred by the rats prior to drug treatment. On three successive days, rats received an intraperitoneal (i.p.) injection of naloxone-HCl (1 mg/kg) or vehicle 15 min before an i.p. injection of either 37 nmol/kg SP, equimolar dosed SPC or corresponding diluent vehicle. After injection the rats were placed into their assigned treatment corral for 15 min. During the test for conditioned corral preference (CCP), when provided a choice between the four quadrants, rats injected with SP or SPC spent more time in the treatment corral compared to vehicle controls, indicative of a positive reinforcing action of these peptides. The pre-treatment with naloxone blocked the positive reinforcing effects of both SP and SPC; when injected alone, naloxone did not influence the preference behavior. Gross locomotor activity was affected by neither treatment. Thus, the positive reinforcing effects of SP and SPC may be mediated via interactions with the endogenous opioid system(s).

Reproducibility of leukotriene D4 inhalation challenge in asthmatics

We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics.

Effect of prior treatment with Clostridium perfringens epsilon toxin inactivated by various agents on lethal, pressor and contractile activities of the toxin

Lethal and pressor activities, and the contractile responses of rai isolated ileum to Clostridium perfrigens epsilon toxin, were significantly prevented by the prior administration of epsilon toxin inactivated by 1-ethyl-3(3-diethyly-aminopropyl) carbodiimide in the presence of glycine methyl ester (EDC), 2,4,6-trinitrobenzene sulfonic acid (TNBS), succinic anhydride (SA) and ethoxyformic anhydride (EFA). Howerver, the prior administration of the toxin inactivated by N-acetylimidazole (NaI), tetranitromethane(TNM) and N-bromosuccinimide (NBS) resulted in no inhibition of these biological activities. These data suggest that the toxin interacts with specific site(s) on target organs or tissues. The relationship between amino acid residues and the actions of the toxin is described.

Effect of prior treatment withClostridium perfringensepsilon toxin inactivated by various agents on lethal, pressor and contractile activities of the toxin

Effect of prior treatment with<i>Clostridium perfringens</i>epsilon toxin inactivated by various agents on lethal, pressor and contractile activities of the toxin

Populations and activity of carbofuran-degrading microorganisms in soil

Kendaia clay loam contained more than 105 microbial cells per g able to convert 14C-carbonyl-labelled carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) to 14CO2 but never more than 130 cells per g transforming 14C-ring-labelled carbofuran to CO2. The sizes of the population rarely increased as a result of addition of the insecticide to soil. Mineralization of these compounds proceeded with little or no acclimation phase, and subsequent additions were usually etabolized more readily, except at 10 mg of carbofuran per kg or if subsequent additions of the pesticide were made long after the first. More than 60% of the 14C in the carbonyl but less of the 14C in the ring was microbiologically converted to 14CO2 in this soil. Streptomycin and cycloheximide each inhibited conversion of the carbonyl or ring carbon to CO2. Urea but not NH4NO3 markedly inhibited the conversion of the carbonyl-labelled insecticide to 14CO2. The addition of glucose and succinate together with the insecticide did not enhance mineralization of ring- or carbonyl-labelled carbofuran. The data suggest that soils containing a large population of microorganisms able to convert the carbonyl carbon to CO2 will not show a marked effect of prior treatment with the insecticide and that few organisms individually are able to mineralize the ring.

A Latent Effect of Us Preexposure in Autoshaping

In two experiments, pigeons were given unsignaled food presentations (Group Unsignaled), tone-food pairings (Group Signaled), or no treatment (Group Control). All groups were subsequently given pairings of a white keylight with food. Although no group differences in autoshaping to white appeared, when birds were subsequently given autoshaping with a different colored light using partial reinforcement, either in a different set of chambers (Experiment 1) or in the same set of chambers (Experiment 2), an effect of prior treatment did appear. Birds in Group Unsignaled responded at a lower rate than those in Groups Signaled and Control, which did not differ.

The infectivity of Schistosoma mansoni in mice, following dipping with an acaricide

The effect of prior treatment of mice with an acaricide (Alugan) on the infectivity of Schistosoma mansoni cercariae via the percutaneous route was assessed. No effects were observed, even in animals dipped only 1 day before exposure to cercariae.

Characterization of the cytochrome P-450 monooxygenase system of hamster liver microsomes: Effects of prior treatment with ethanol and other xenobiotics

The cytochrome P-450 monooxygenase system of hamster liver microsomes and its response to prior treatment with ethanol and other xenobiotics have been examined. Male Syrian golden hamsters were administered ethanol (ETOH), phenobarbital (PB), 5,6-benzoflavone (BF) or isoniazid (INH). Each treatment resulted in a moderate increase (20–60%) in the specific content of liver microsomal cytochrome P-450 along with a unique hemeprotein ferrous carbonyl Soret maximum. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of liver microsomes revealed distinctive changes in protein banding patterns in the cytochrome P-450 (45–60 kDa) region with each treatment. NADPH : cytochrome c reductase activity was increased by both PB and INH, whereas cytochrome b 5 content was increased by INH only. Microsomal oxidation of ETOH and aniline p-hydroxylation (expressed per nmol cytochrome P-450) were enhanced dramatically by ETOH and INH, whereas PB and BF had no effect on these enzymatic activities. Both ETOH and INH also increased zoxazolamine 6-hydroxylation but, in contrast to other rodent species, this drug-metabolizing activity was decreased in hamster liver microsomes after treatment with either PB or BF. Microsomal benzphetamine N-demethylation was decreased by ETOH, INH and BF administration and was only modestly enhanced after treatment with PB. ETOH and INH had no effect on the O-dethylation of 7-ethoxycoumarin, and enzymatic activity increased by BF but decreased by PB. These results demonstrate that the cytochrome P-450-dependent monooxygenase system of hamster liver microsomes responds to treatment with ETOH and other xenobiotics in a manner that is quantitatively and, in certain respects, qualitatively different from that reported for the rat, rabbit, and mouse.