Sensitivity Of Peripheral Blood Lymphocytes Research Articles

SENSITIVITY TO 4-HYDROXYESTRADIOL AND DNA REPAIR EFFICIENCY IN PERIPHERAL BLOOD LYMPHOCYTES OF ENDOMETRIAL CANCER PATIENTS

The development of hormone-dependent cancers, including endometrial carcinomas, in great part may be mediated by the genotoxic effects of estrogen metabolites, among which 4-hydroxyestradiol (4OHE2) is characterized by the most prominent DNA-damaging properties. It is assumed that the individual sensitivity to the 4OHE2may determine the predisposition to endometrial cancer (EС). To analyze the sensitivity of peripheral blood lymphocytes (PBLs) of EC patients to the 4OHE2and to evaluate the repair efficiency of 4OHE2-induced DNA damage. The study was performed on the PBLs of 53EC patients and 20healthy women. The level of DNA damage was measured using the comet assay and was expressed as% tail DNA. The DNA repair efficiency (%) was evaluated by determining the ratio between the amount of repaired DNA damage and the level of 4OHE2-induced damage that appeared after incubation of PBLs with 4OHE2. In PBLs of EC patients, a higher level of 4OHE2-induced DNA damage (32.0 ± 2.2% tail DNA) and lower DNA repair efficiency (34.0 ± 4.5%) was observed compared to PBLs of healthy women (22.3 ± 2.3% tail DNA and 48.8 ± 4.5%, respectively). PBLs of EC patients with deep tumor invasion of myometrium were characterized by more prominent decrease of DNA repair than those with less invasive tumor (<½of myometrium) (20.9 ± 7.8 and 43.7 ± 6.7%, respectively). Furthermore, lower DNA repair efficiency was detected in the PBLs of EC patients with a family history of cancer compared to this parameter in patients with sporadic tumors (20.9±7.8and 47.1 ± 5.5%, respectively). The PBLs of EC patients are characterized by increased sensitivity to the genotoxic effect of 4OHE2and reduced repair efficiency regarding 4OHE2-induced DNA damage. A lower level of DNA repair is observed in EC patients with deep tumor myometrial invasion and a family history of cancer.

Higher Sensitivity of Peripheral Blood Lymphocytes to Endogenous Glucocorticoid in Renal Transplant Recipients Treated with Tacrolimus, as Compared to Those Treated with Cyclosporine

Background: Steroids in maintenance immunosuppressive drugs produce severe adverse events, and therefore, the use of steroids is withdrawn for many renal transplant recipients. However, steroids need to be restarted to prevent the worsening of renal function because of rejection episodes in some patients or in patients who experience steroid withdrawal syndrome. Currently, there are no indicators to predict which patients can sustain steroid withdrawal. Lymphocyte sensitivity to endogenous glucocorticoid cortisol could be a biological marker for safety reduction and steroid withdrawal. We examined relationship between lymphocyte sensitivity to cortisol in vitro and clinical outcome after steroid reduction or withdrawal in the renal transplant recipients. We also compared peripheral lymphocyte sensitivity to cortisol between transplant recipients treated with tacrolimus (Tac) and those treated with cyclosporine. Methods: The suppressive efficacies of cortisol against T-cell mitogen stimulated proliferation of peripheral lymphocytes was investigated in totally 41 patients with renal tramsplant patients, who were reducedor withdrawnsteroid. Nineteen out of the 41 patients were treated with Tac and the other 22 patients with cyclosporine A (CyA). Relationship between lymphocyte sensitivity to cortisol invitro and clinical outcome after steroid reduction or withdrawal was evaluated in 30 out of 41 renal transplant recipients. The lymphocyte sensitivity to cortisol was compared between 19 patients treated with Tac and 22 patients treated with CyA. Results: The cortisol IC50 values in the Tac and CyA groups were 0.09 ± 0.12 and 14.2 ± 12.7ng/ml, respectively. Lymphocyte sensitivity to cortisol in the Tac-treated group was significantly higher than that in the CyA treated group (p =0.0283). On the other hand, incidences of steroid withdrawal syndrome and increase in serum creatinine concentration were not significantly different between the Tac and CyA groups. Lymphocyte sensitivity to cortisol and its relationship with the clinical outcome after steroid reduction and withdrawal was investigated in 30 long stable renal transplant recipients. Serum creatinine levels increased in a significantly higher number of patients with lymphocytes hyposensitive to cortisol (IC50 ≥ 10000 ng/mL) than in normally sensitive patients (IC50 < 10000 ng/mL) (P < 0.005). The incidences of steroid withdrawal syndrome (P< 0.05) and necessity for increasing steroid dose or restarting steroid administration (P< 0.005) were also higher in the patients hyposensitive to cortisol than in normally sensitive patients. The patients in whom the lymphocyte proliferation rate was less than 60% did not show increase in S-Cr levels, experience steroid withdrawal symptoms, or require an increase in the steroid dose or restart of steroid administration. Conclusion: We considered from these observations that the lymphocyte sensitivity to cortisol would be useful for selecting patients for whom steroids should be withdrawn, and as a biomarker to safely reduce and withdraw steroids. Lymphocyte sensitivity to cortisol was higher in the Tac treated patients than that in the CyA treated ones. Since the cortisol sensitivity of peripheral lymphocytes is suggested to be a predictive marker for safe steroid withdrawal as described above, Tac administration shows promise in aiding successful withdrawal of steroid in long-term renal transplant recipients.

Higher Sensitivity of Peripheral Blood Lymphocytes to Endogenous Glucocorticoid in Renal Transplant Recipients Treated With Tacrolimus, as Compared to Those Treated With Cyclosporine.

Lymphocyte sensitivity to endogenous glucocorticoid cortisol could be a biological marker for safe reduction and withdrawal of steroids in renal transplant recipients. We compared peripheral lymphocyte sensitivity with cortisol between transplant recipients treated with tacrolimus (Tac) and those treated with cyclosporine. The suppressive efficacies of cortisol against T-cell mitogen-stimulated proliferation of peripheral lymphocytes were investigated in 44 renal transplant patients, who either had reduced or been withdrawn from steroid treatment. Twenty of the 44 patients were treated with Tac, and the other 24 patients were treated with cyclosporine A (CyA). The lymphocyte sensitivity to cortisol was compared between these two patient groups. The cortisol IC50 values in the Tac and CyA groups were 0.09 ± 0.12 and 14.2 ± 12.7 ng/ml, respectively. Lymphocyte sensitivity to cortisol in the Tac-treated group was significantly higher than that in the CyA-treated group (p = 0.0283). On the other hand, incidences of steroid withdrawal syndrome and increases in serum creatinine concentration were not significantly different between the Tac and CyA groups. Lymphocyte sensitivity to cortisol was higher in the Tac-treated patients than that in the CyA-treated ones. Since the cortisol sensitivity of peripheral lymphocytes is suggested to be a predictive marker for safe steroid withdrawal, Tac administration shows promise in aiding successful withdrawal of steroid treatment in long-term renal transplant recipients.

Are thyroid cancer patients sensitive to ionising radiation?

Purpose: To determine the ionising radiation sensitivity of peripheral blood lymphocytes in a group of differentiated thyroid cancer (DTC) patients.Material and methods: A total of 53 thyroid cancer patients (26 women and 27 men) and 50 donors (23 women and 27 men) were included in the study. The cytokinesis-block micronucleus assay (CBMN) in G0 peripheral blood lymphocytes was carried out using the cytochalasin B technique. Four cultures were established per each donor, two were irradiated with 0.5 Gy 137Cs g-rays, while the other two remained untreated.Results: No significant differences were observed in the frequency of binucleated cells with micronuclei (BNMN) between patients and controls, for both spontaneous and after the irradiation frequencies. Nevertheless, a positive and significant correlation was found between the frequencies of both spontaneous and after irradiation DNA damage, for control and patient groups.Conclusions: We have found that DTC patients do not present particular sensitivity to ionising radiation when an in vitro treatment is performed in G0 stage of the cell cycle, but this result does not discard the hypothesis about an increased sensitivity in other stages of the cell cycle in DTC patients.

Sensitivity of peripheral blood lymphocytes of pilots and astronauts to γ-radiation: Induction of double-stranded DNA breaks

The levels of DNA breaks before and after in vitro irradiation (1 Gy) of lymphocytes from 17 donors, 41 pilots, and 8 astronauts were studied by comet assay. Seventeen donors. 41 pilots, and 8 astronauts were examined. The flights augmented individual differences in the levels of DNA breaks in blood lymphocytes and in the severity of injuries inflicted by radiation exposure to lymphocyte DNA. Dispersions in the distribution of the initial levels of DNA breaks in pilots and astronauts differed significantly from the control according to Fisher's F test. The dispersion of distribution of the levels of double-stranded DNA breaks after in vitro irradiation in the group of pilots also differed significantly from the control distribution. These results necessitate evaluation of individual sensitivity to the mission conditions during medical selection.

Systemic sensitivity to corticosteroids in smokers with asthma

Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.

Effects of Smoking Cessation on Lung Function and Airway Inflammation in Smokers with Asthma

Active smoking in asthma is associated with worsening of symptoms, accelerated decline in lung function, and impaired response to corticosteroids. To examine the short-term effects of smoking cessation on lung function, airway inflammation, and corticosteroid responsiveness in smokers with asthma. Smokers with asthma were given the option to quit or continue smoking. Both groups underwent spirometry and induced sputum at baseline and at 1, 3, and 6 wk. Cutaneous vasoconstrictor response to topical beclometasone, airway response to oral prednisolone, and sensitivity of peripheral blood lymphocytes to corticosteroids were measured before smoking cessation and at 6 wk. Of 32 subjects recruited, 11 opted to continue smoking (smoking control group). Of 21 subjects who opted for smoking cessation, 10 quit smoking for 6 wk (quit group). In the comparison of quitters with smokers at 6 wk, the mean (confidence interval [CI]) difference in FEV(1) was 407 ml (21, 793), p = 0.040, and the proportion of sputum neutrophils was reduced by 29 (51, 8), p = 0.039. Total cutaneous vasoconstrictor response score to topical beclometasone improved after smoking cessation with a mean (CI) difference of 3.56 (0.84, 6.28), p = 0.042, between quitters and smokers. There was no change in airway corticosteroid responses after smoking cessation. By 6 wk after smoking cessation, subjects who quit smoking had achieved considerable improvement in lung function and a fall in sputum neutrophil count compared with subjects who continued to smoke. These findings highlight the importance of smoking cessation in asthma.

Sensitivity of peripheral blood lymphocytes from breast cancer patients to glucocorticoids

We measured DNA-dependent RNA polymerase activity, calculated hormone-binding sites and intracellular association constant under conditions of phytohemagglutinin stimulation and dexamethasone treatment, and studied the interaction of cells with the glucocorticoid covalently bound to an inert carrier not penetrating into cells. Reduced sensitivity of peripheral blood lymphocytes from breast cancer patients to glucocorticoids was demonstrated. The biological mechanisms for hormonal regulation are reviewed here.

Apoptosis of Peripheral Human Blood Lymphocytes Induced by Physical‐Chemical Influences and Generation of Reactive Oxygen Species

The sensitivity of peripheral blood lymphocytes of healthy people (blood donors) to induced apoptotic processes and reactive oxygen species production under physical-chemical influences was evaluated in vitro.

Lymphocyte Drug Sensitivity Is Useful for Prediction of the Antiproteinuric Effect and Relapse Rate in Cyclosporine Treatment for Frequent-Relapse Minimal Change Nephrotic Syndrome

Background/Aims: The therapeutic effect of cyclosporine A (CsA) in combination with steroids varies greatly for frequent-relapse minimal change nephrotic syndrome (FRMCNS). The association between the sensitivity of peripheral blood lymphocytes (PBLs) to CsA in vitro and the therapeutic effect of CsA in FRMCNS were investigated. Methods: The sensitivity of PBLs in vitro and the therapeutic effect of CsA in 23 FRMCNS patients were compared. The length of time to complete remission (CR) and the number of relapses were compared using the 50% inhibitory concentration (IC₅₀) of CsA in the presence of a T-cell mitogen. Results: FRMCNS patients were divided into 2 groups: a low sensitivity group with an IC₅₀ of >14.8 ng/ml (GII, n = 10), and a high sensitivity group with an IC₅₀ of <14.8 ng/ml (GI, n = 13). Comparison of the length of time to CR between the 2 groups showed that GI reached CR earlier than GII (p < 0.01). GI had significantly fewer relapses than GII when CsA was administered for 12 months or longer (p < 0.01). Conclusion: Lymphocyte sensitivity to CsA has the potential to be an important clinical indicator of the antiproteinuric effect and relapse rate in FRMCNS.

Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide

Epstein-Barr virus (EBV) is associated with several types of malignancies including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and gastric carcinoma. Previous reports have suggested that EBV-related antigen-targeting immunotherapy is one of the promising approaches for the treatment of these malignancies other than gastric carcinoma. EBV-associated gastric carcinoma (EBVaGC) has been shown to express Epstein-Barr virus nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). In the present study, DNA and mRNA freshly isolated from tumors of patients with gastric cancer were subjected to polymerase chain reaction (PCR) using EBV-specific primers and reverse transcription (RT)-PCR specific for LMP2 transcripts. EBV-specific region was identified in genomic DNA isolated from cancerous tissues in 22% of gastric cancer patients. LMP2 mRNA was also detected in 3 out of these 5 DNA positive samples tested. To investigate the feasibility of specific immunotherapy for EBVaGC, we induced cytotoxic T lymphocytes (CTLs) from peripheral blood lymphocytes using two kinds of antigen-presenting cells (APCs) such as autologous lymphoblastoid cell line (LCL) and LMP2-derived peptide-pulsed dendritic cells (DCs). The cytotoxicity of these CTLs against peptide-pulsed targets was examined by standard 51Cr release assay and interferon (IFN)-gamma production assay. We further assessed the recognition of tumor cells endogenously expressing LMP2 by these T cells. T cells induced by peptide-loaded DCs and autologous LCL efficiently lysed peptide-pulsed targets. Furthermore, these T cells could recognize not only tumor cells transfected with LMP2, but also LMP2-positive gastric cancer cells which were successfully isolated and cultured from specimens obtained by surgery. Collectively, sensitization of peripheral blood lymphocytes with LMP2-derived peptide was able to induce CTL response against EBVaGC cells. Thus, EBVaGC is susceptible for the LMP2-targeting immunotherapy.

Effect of vitamin therapy on sensitivity of peripheral blood lymphocytes to clastogenic effect of mutagens in vitro.

Spontaneous and in vitro induced (with 0.01 and 0.1 mg/ml dioxidine and 0.1 and 1.0 U/ml bleomycin) chromosome aberrations were counted in cultured peripheral blood cells from 11 donors before and after 2-week therapy with a vitamin complex. The complex contained the major vitamins in doses not surpassing the recommended daily doses. Vitamins had no effect on spontaneous mutations, but increased cell resistance to clastogenic effects of dioxidine in a concentration of 0.1, but not 0.01 mg/ml. Cell sensitivity to bleomycin notably increased after vitamin therapy in some donors and decreased in others, the mean parameters in the group remained virtually unchanged.

Markers of cell death-activation in lymphocytes of vertically HIV-infected children naive to highly active antiretroviral therapy: The role of age

Background: Apoptosis plays a major role in depleting CD4+ lymphocytes during infection with HIV-1. Few data exist on its role during HIV infection of children. Sensitivity of peripheral blood lymphocytes (PBLs) to apoptotic stimuli and the importance of the patient’s age remain unclear. Objectives: We sought to analyze the following: (1) markers of cell death-activation (CD95, CD45 isoforms, and CD28) in PBLs from vertically HIV-infected children of different ages before highly active antiretroviral therapy; (2) changes in other PBL populations; (3) PBL sensitivity to cell death and mitochondrial damages; and (4) role of age during progression of infection. Methods: Cell culture techniques and flow cytometry were used to analyze surface antigens, PBL susceptibility to apoptosis, or PBL susceptibility to change of mitochondrial membrane potential. Results: Donor age had a strong negative correlation with numbers of CD4+ and CD8+ T cells. Virgin T lymphocyte (CD45RA+, CD95–) levels and those of CD95+ cells showed no correlation with the children’s clinical status but did show a correlation with patient age. CD28– T lymphocytes were markedly augmented in HIV-infected children but were unrelated to stage of infection or age. A relevant decrease in B lymphocytes and an increase in natural killer cells were also found. Finally, PBLs from HIV-positive children had a marked tendency to undergo apoptosis and mitochondrial damage. Conclusion: Changes in PBL phenotype, increased expression of CD95, and high sensitivity to apoptosis suggest that a precocious aging of the immune system occurs in HIV-infected children. (J Allergy Clin Immunol 2001;108:439-45.)

Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay

Carcinogenesis in the upper aerodigestive tract is influenced by multiple factors. Besides tobacco and alcohol consumption, specific pollutants such as phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be important in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to investigate whether human peripheral blood lymphocytes and mucosal epithelium of the upper aerodigestive tract, the target for volatile and liquid xenobiotics, are equally sensitive to genotoxic agents. The Comet assay was used to detect for DNA damage induced by genotoxic agents in mucosal epithelial cells and peripheral blood lymphocytes of 60 volunteers. Mucosa was harvested from larynx, oropharynx, and inferior nasal turbinates. Xenobiotics investigated were dibutylphthalate (DBP), diisobutylphthalate (DiBP), N′-nitrosodiethylamine (NDELA), benzo[ a]pyrene (B[ a]P), and N′-methyl- N′-nitro- N-nitrosoguanidine (MNNG). DBP, DiBP, B[ a]P, NDELA and MNNG induced a significant increase in DNA migration in both cell populations. Peripheral blood lymphocytes were more sensitive than mucosal cells to DBP and DiBP, but not to NDELA and B[ a]P. The correlation, in terms of DNA migration, between lymphocytes and mucosal cells among volunteers was relatively poor. Based on the poor correlation in response between the two cell types, the sensitivity of peripheral blood lymphocytes to genotoxic agents appears to be a poor predictor of sensitivity in the target cells of the upper aerodigestive tract. Further attention should be focused on intra-individual mutagen sensitivities and inter-individual genetic differences as regards susceptibility to upper aerodigestive tract cancer.

Preoperative ATG bolus treatment increase CsA sensitivity of peripheral blood lymphocytes (PBLS) in renal transplant patients

Preoperative ATG bolus treatment increase CsA sensitivity of peripheral blood lymphocytes (PBLS) in renal transplant patients

Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans.

Although plasma corticosteroid concentrations can be measured accurately, the biological effect on the target tissue is uncertain. The availability of an accurate measure of corticosteroid sensitivity would potentially clarify the putative roles of endogenous glucocorticoids in illnesses such as inflammatory disease and obesity and allow evaluation of an additional regulatory level of glucocorticoid action. To measure corticosteroid sensitivity, we developed an assay based on the inhibition by dexamethasone (Dex) of lipopolysaccharide (LPS)-induced Interleukin-6 (IL-6) production and release in whole unseparated blood in vitro. LPS induced a dose-dependent increase in IL-6 concentrations up to 34 +/- 6.6 ng/mL, reaching plateau levels after 8 h, whereas Dex dose dependently inhibited LPS-induced IL-6 production. Involvement of the glucocorticoid receptor in this response was supported by abrogation of Dex (10(-7) mol/L) inhibition of IL-6 production by the glucocorticoid receptor antagonist RU 38486. To determine whether corticosteroid sensitivity is a dynamic phenomenon, we subjected healthy males to a graded quantifiable exercise associated with increases in plasma ACTH and cortisol. Before exercise, 3 x 10(-8) mol/L Dex inhibited LPS-induced IL-6 production in vitro; after exercise, 3 x 10(-8) and 10(-7) mol/L Dex were unable to inhibit IL-6 production. We conclude that Dex suppression of LPS-induced IL-6 production is an effective means of determining corticosteroid sensitivity, and that corticosteroid sensitivity in human subjects is a dynamic, rather than a static, phenomenon.

Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans

Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans

IFN-ALPHA THERAPY OF RENAL-CELL CARCINOMA - DEFECT OF LYMPHOCYTE SENSITIVITY TO MITOGENIC AND ACTIVATING CYTOKINE SIGNALS IN PATIENTS NOT-RESPONDING TO THERAPY

The present prospective study was designed to assess whether the renal cell carcinoma (RCC) patients treated with recombinant interferon alpha (IFN alpha), whose tumours respond (responders) and do not respond (non-responders) to IFN alpha therapy, differ with regard to in vitro sensitivity of peripheral blood lymphocytes (PBL) to interleukin 2 (IL-2), IFN alpha, and IFN gamma signals prior to therapy. Twenty-one patients with advanced RCC after nephrectomy, 15 responders and 6 non-responders, were entered into a protocol. The protocol involved isolation and freezing of PBL samples followed by IFN alpha treatment of patients, assessment of proliferative and activating PBL responses, and evaluation of the therapeutic results. Freezing of PBL samples allowed us to compare the in vitro reactivity of PBL from individual RCC patients, repeatedly and under standard conditions. Substantial differences in proliferative responses to the mitogenic IL-2 signal of PBL derived from IFN alpha responders and nonresponders were found. Whereas the IL-2-induced proliferative responses of PBL from normal blood donors and IFN alpha responders were comparable, the proliferative responses of PBL from IFN alpha non-responders were significantly decreased, suggesting an immune dysfunction in non-responders. Cultivation of PBL from RCC patients in medium supplemented with IFN alpha increased the lytic activity of PBL from IFN alpha responders directed against RCC targets; no such increase could be observed with non-RCC targets, with PBL from IFN alpha non-responders, or with PBL from normal blood donors. Detection of phytohaemagglutinin (PHA)-stimulated IFN gamma secretion by PBL at the single cell level using enzyme-linked immunospot (ELISpot) assay revealed that the ability to produce IFN gamma was substantially decreased in IFN gamma non-reponders, as compared to IFN alpha responders and to normal blood donors.

Differential sensitivity of peripheral blood lymphocytes of untreated leprosy patients to mitomycin C

The effects of a bifunctional alkylating agent mitomycin C (MMC), an effective inducer of chromosome aberrations and sister-chromatid exchanges (SCEs), have been studied in untreated leprosy patients. This was done to study the mutagen sensitivity of the leprosy patients. The frequency of chromosomal aberrations induced by MMC (conc. 0.01 μg/ml) was 2.5% in controls, 3.6% in paucibacillary (PB), and 6.8% in multibacillary (MB) patients. The difference in the frequency of MMC-induced chromosome aberrations between the 3 groups studied was highly significant ( p < 0.01). Cultures grown with MMC showed the frequency of SCEs/cell to be 12.70 ± 1.19 in controls, 19.97 ± 3.51 in PB, and 29.66 ± 5.92 in MB patients. The differences in the frequency of MMC-induced SCEs between the 3 groups were found to be highly significant ( p < 0.01). The enhanced frequencies of spontaneous and MMC-induced chromosome aberrations and SCEs observed in PB and MB patients indicate a clear differential mutagen sensitivity between PB and MB patients who are known to have different immunological status and thereby differ in the severity of the disease.

Gamma-Radiation and Mitomycin C Sensitivity of Peripheral Blood Lymphocytes from Saudi Patients with Non-Hodgkin’s Lymphoma

Peripheral blood lymphocytes (PBLs) from 28 patients with non-Hodgkin's lymphoma (NHL) were compared with those of 28 healthy subjects (controls) for their responsiveness to the T cell mitogen phytohemagglutinin (PHA) before and after treatment with gamma-radiation and mitomycin C. PBLs from 9 of the 28 patients with NHL exhibited almost a total failure to respond to PHA while mitogenic stimulation in the rest varied from 7 to 90% relative to the controls. PBLs from 19 NHL patients and 28 healthy subjects were compared for their radiosensitivity by measuring postirradiation uptake of [3H]-thymidine. Increased sensitivity to gamma-radiation was observed in more than half of the NHL patients studied. Increased sensitivity to mitomycin C was also noted in 5 of the 7 patients analyzed compared to the respective controls. Poor mitogenic responsiveness and hypersensitivity of blood lymphocytes to the carcinogens (gamma-rays and mitomycin C) are suggestive of a severe immunological abnormality and defective DNA repair in these Saudi NHL patients.