scholarly journals Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 731
Author(s):  
Eduardo Naranjo-Vázquez ◽  
María Guadalupe Sánchez-Parada ◽  
Belinda Claudia Gómez-Meda ◽  
Ana Lourdes Zamora-Perez ◽  
Martha Patricia Gallegos-Arreola ◽  
...  
Keyword(s):  
Dna Damage ◽  
Peripheral Blood ◽  
Micronucleus Assay ◽  
Control Group ◽  
High Dose ◽  
Entire Body ◽  
Hairless Mice ◽  
Mutagenic Potential ◽  
Polychromatic Erythrocytes ◽  
High Doses

SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect.

Investigation of Effects of Silymarin in 5-Fluorouracil Hepatotoxicity and Nephrotoxicity in Mice

2021 ◽  
Author(s):  
Emin Sengul ◽  
Volkan Gelen ◽  
Serkan Yildirim ◽  
Esra Senturk ◽  
Yusuf Dag ◽  
...  
Keyword(s):  
Dna Damage ◽  
Side Effects ◽  
Total Bilirubin ◽  
Control Group ◽  
High Dose ◽  
Liver And Kidney ◽  
Group 5 ◽  
High Doses ◽  
Kidney Functions ◽  
Liver And Kidney Damage

Abstract Hepatotoxicity and nephrotoxicity are common side effects of 5-Fluorouracil (5-FU). The present study aimed to investigate the effects of Silymarin (SLY) on 5-FU induced hepatotoxicity and nephrotoxicity in mice. In our study, 10 mice in each group were randomly divided into four groups as the control group, 5-FU, SLY50+5-FU, and SLY100+5-FU group. SLY50+5-FU and SLY100+5-FU groups were administered at a dose of 50 and 100 mg/kg for seven days, respectively. 5-FU was administered at a dose of 400 mg/kg intraperitoneally on the fourth day. After the applications, the mice were decapitated under anesthesia. The liver and kidney functions which urea, creatinine, AST, ALT, and total bilirubin levels were analyzed in serum. In liver and renal tissues, MDA and GSH levels, SOD, CAT, and GR activity were determined. Also, histopathological and immunohistochemical changes were examined in liver and kidney sections. Urea, creatinine, ALT, AST, and total bilirubin levels increased 5-FU group according to control and prevented to this increases the especially high dose of SLY. 5-FU also causes histopathological and immunohistochemical changes such as degeneration, necrosis, hyperemia, DNA damage, and IL-6 increase in kidney and liver tissue. High doses of SLY prevented these changes caused by 5-FU. As a result of this study, it was determined that SLY has hepatoprotective and nephroprotective effects on 5-FU-induced liver and kidney damage in mice.

scholarly journals Assessment of DNA damage through micronucleus studies in subjects exposed to formalin

2021 ◽  
Vol 19 (1) ◽  
pp. 01-05
Author(s):  
K Sriambika ◽  
Keyword(s):  
Dna Damage ◽  
Peripheral Blood ◽  
Micronucleus Assay ◽  
Peripheral Blood Lymphocytes ◽  
International Agency ◽  
Control Group ◽  
Buccal Cells ◽  
Exposed Workers ◽  
The Mean ◽  
The Relationship

Background: Formaldehyde (FA) is the reactive and simplest of all the aldehydes. It is used as a preservative in anatomy, pathology and forensic laboratories. The international agency for research on cancer has classified FA as a carcinogen that can cause nasopharyngeal carcinoma, Leukaemia, Liver and pancreatic cancer. Objective And Method: The aim of the study was to assess the DNA damage in peripheral blood lymphocytes and in buccal cells by Micronucleus assay in Formalin exposed workers of Anatomy, Pathology and Forensic laboratories and compare with the control group, and also to analyze the relationship between frequency of Micronuclei and duration of exposure to formalin. Results: The mean and standard deviation (SD) of micronuclei in peripheral blood of exposed was 8.35 and in controls was 4.18. There was a significant increase in the frequency of MN in exposed group when compared with the comparison group (p<0. 5876). Pearson’s correlation test showed a positive correlation between the years of FA exposure and the number of micronuclei in buccal cells and peripheral blood indicating that DNA damage due to FA was directly proportional to the duration of exposure (r=0.8, 0.9). Conclusion: The present study was done to assess the DNA damage in people who were exposed to FA and a control group not exposed to FA by buccal cell and peripheral blood Micronucleus Assay. There was a significant increase in the MN in people exposed to FA which was directly proportional to the duration of exposure.

Evaluation of genotoxicity of pan masala employing chromosomal aberration and micronucleus assay in bone marrow cells of the mice

2009 ◽  
Vol 25 (7) ◽  
pp. 467-471 ◽  
Author(s):  
BN Mojidra ◽  
K. Archana ◽  
AK Gautam ◽  
Y. Verma ◽  
BC Lakkad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosome Aberration ◽  
Chromosomal Aberration ◽  
Bone Marrow Cells ◽  
Micronucleus Assay ◽  
Control Group ◽  
Genotoxic Potential ◽  
Polychromatic Erythrocytes ◽  
Significant Difference ◽  
Marrow Cells

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

scholarly journals Persistent Increased Frequency of Genomic Instability in Women Diagnosed with Breast Cancer: Before, during, and after Treatments

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
André Luiz Pinho Sobral ◽  
Jaqueline Nascimento Picada ◽  
Ivana Grivicich ◽  
Antonio Luiz Gomes Júnior ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Comet Assay ◽  
Peripheral Blood ◽  
Micronucleus Test ◽  
Cancer Control ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Buccal Cells ◽  
Oncological Treatment

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient’s cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.

scholarly journals Genotoxic evaluation of ceftriaxone by in vivo micronucleus test in albino mice

2018 ◽  
Vol 7 (9) ◽  
pp. 1705
Author(s):  
Kunjumon Dayana ◽  
Megaravalli R. Manasa
Keyword(s):  
Bone Marrow ◽  
Micronucleus Test ◽  
Micronucleus Assay ◽  
Generation Cephalosporin ◽  
New Drugs ◽  
Control Group ◽  
Genotoxic Potential ◽  
Polychromatic Erythrocytes ◽  
Albino Mice

Background: Genotoxicity screening of drugs is essential. It is mandatory for new drugs. However, screening of drugs already in use is also necessary. Several cephalosporins are reported to induce chromosomal aberrations in previous studies. But there is paucity of data regarding the genotoxic potential of ceftriaxone. Hence the present study was undertaken to evaluate the genotoxic potential of ceftriaxone, a third generation cephalosporin, by micronucleus assay in albino mice.Methods: In vivo micronucleus test was performed with mice bone marrow after intraperitoneal injection of ceftriaxone at 100mg/kg BW and 200mg/kg BW at 24 hr and 48 hr harvest time. Mice bone marrow was harvested, and slides were prepared. The percentage of micronucleated polychromatic erythrocytes (% MnPCE) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE:NCE) were determined. The data from ceftriaxone treated groups was compared with control group and analyzed using ANOVA followed by Dunnett's test.Results: Ceftriaxone at the dose of 100mg/kg BW and 200mg/kg BW did not exhibit any significant increase in the percentage of micronucleated polychromatic erythrocytes. It also did not decrease the ratio of polychromatic erythrocytes to normochromatic erythrocytes significantly.Conclusions: The present study demonstrates that ceftriaxone is not genotoxic in in vivo micronucleus study in albino mice at a dose of 100mg/kg BW and 200mg/kg BW.

Chemotherapy-Induced T-MDS/AML-Associated Genetic Aberrations.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2021-2021
Author(s):  
Joerg Baesecke ◽  
Martina Podleschny ◽  
Julia Goldstein ◽  
Claudia Riechel ◽  
Detlef Haase ◽  
...  
Keyword(s):  
Cord Blood ◽  
Peripheral Blood ◽  
Early Recognition ◽  
Genotoxic Stress ◽  
High Dose Chemotherapy ◽  
Ongoing Study ◽  
Control Group ◽  
High Dose ◽  
Fish Analysis ◽  
Genetic Aberrations

Abstract Therapy-related solid and hematological neoplasias occur according to the treatment regimen and intensity. The cumulative incidence of therapy related myelodysplastic syndromes and acute myeloid leukemias(t-MDS/AML) ranges between 5 and 15% in non-myeloablative and myeloablative treatment protocols respectively. t-MDS/AML share characteristic genetic aberrations which include translocations (e.g. involving 11q23, MLL and t(9;22), inv 16, t(8;21), t(3;21), t(15;17) and cytogenetic aberrations (e.g. 5q-, 7q-). We have investigated if these genetic aberrations are present in patients who underwent chemotherapy. Since we and others have detected aberrations in aleukemic hematopoiesis (Baesecke et al. Blood. 2002;100:2267–2268) we also wanted to determine if t-MDS/AML early recognition can be performed by this screening. We enrolled patients with Non Hodgkin Lymphoma, either treated by conventional or high dose chemotherapy, included in the MegaChoep protocoll of the German high grade lymphoma study group. Samples were taken as fresh peripheral blood stem cells (PBSCT), bone marrow aspirates (BM) or peripheral blood (PB) after informed consent according to the convention of Helsinki. PBSC of healthy adult donors and cord blood of healthy newborn were used as control. Blood samples were submitted to RT- or Real-Time PCR (sensitivity 10–4 to 10–5) of t(9;22), inv 16, t(8;21), t(15;17) and MLL-partial tandem duplications (MLL-PTD). RNA preparation, reverse transcription, and PCR were performed in separate laboratories. Cytogenetic analysis was performed by FISH (probes EGR1-del5, p53, cep7-del 7, MLL and cep8-tris 8). The results of the ongoing study are as follows. In the cord blood control group, positive samples were t(15;17) 1.7% (1/60 samples), inv 16 5.6% (3/54), t(8;21) 2.8% (1/36), t(9;22) 3.4% (2/59), MLL-PTD primary PCR 0% (0/34). No positive results were observed in PBSC samples of healthy donors (22 samples). 53 samples of patients of which 21 were PBSC and 32 were BM or PB have been investigated so far. 34/53 patients (64.2%) underwent a high dose chemotherapy. In 9.4% (5/53) the translocation t(15;17) was detected. All five samples were PBSC. No amplification of inv 16, t(8;21) and t(9;22) was observed. In FISH analysis two of 18 patient PBSC samples (11%) exhibited aberrations in the p53 locus, which were classified as abnormal but still non-clonal. Our results confirm the existence of AML-associated translocations in cord blood at frequencies, which by far exceed the incidence of AML in healthy individuals. Compared to these findings the incidence of t-AML- associated aberrations in patients who underwent chemotherapy-induced genotoxic stress is lower than expected. Positive PCR-results of this group may thus be more informative concerning the detection of a leukemic clone and the risk of attracting a t-MDS/AML. Positive patients are currently under observation and the number of samples and aberrations in the ongoing study is increased.

Improving Clinical Outcomes from Acute Subdural Hematomas with the Emergency Preoperative Administration of High Doses of Mannitol: A Randomized Trial

Neurosurgery ◽  
2001 ◽  
Vol 49 (4) ◽  
pp. 864-871 ◽  
Author(s):  
Julio Cruz ◽  
Giulio Minoja ◽  
Kazuo Okuchi
Keyword(s):  
Clinical Outcomes ◽  
Control Group ◽  
High Dose ◽  
Global Brain Ischemia ◽  
Conventional Dose ◽  
Cerebral Hyperperfusion ◽  
Subdural Hematomas ◽  
Postoperative Control ◽  
Cerebral Extraction Of Oxygen ◽  
High Doses

Abstract OBJECTIVE To evaluate clinical outcomes and postoperative physiological findings for comatose patients with acute subdural hematomas who received preoperative high-dose mannitol (HDM) versus conventional-dose mannitol treatment. METHODS One hundred seventy-eight adult patients with non-missile, traumatic, acute, subdural hematomas were prospectively and randomly assigned to receive emergency, preoperative, intravenous HDM treatment (91 patients), compared with a control group treated with a lower preoperative mannitol dose (87 patients). RESULTS Preoperative improvement of abnormal pupillary widening was significantly more frequent in the study group than in the control group of patients (P &lt; 0.0001). Preoperative HDM treatment was also associated with significantly better clinical outcomes at 6-month follow-up evaluations (P &lt; 0.01). Postoperative physiological findings revealed statistically significant between-group differences, with higher intracranial pressure and lower cerebral extraction of oxygen (relative cerebral hyperperfusion) in the control group, compared with the HDM group. Postoperative global brain ischemia (abnormally low arteriojugular lactate difference values) was rare and was detected in 2.2 and 3.4% of the patients in the study and control groups, respectively. CONCLUSION Emergency preoperative HDM administration was associated with improved clinical outcomes for patients with acute subdural hematomas. Preoperative improvement of abnormal pupillary widening and better postoperative control of intracranial hypertension and associated relative cerebral hyperperfusion seemed to be relevant factors associated with improved outcomes.

scholarly journals ANALISIS KERUSAKAN DNA PADA SEL LIMFOSIT PASIEN PASCA-RADIOTERAPI

2021 ◽  
Vol 8 (1) ◽  
pp. 105-113
Author(s):  
Darlina Yusuf ◽  
Devita Tetriana ◽  
Tur Rahardjo ◽  
Teja Kisnanto ◽  
Yanti Lusiyanti ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Dose ◽  
Peripheral Blood ◽  
Tail Length ◽  
Peripheral Blood Lymphocytes ◽  
Comet Tail ◽  
Blood Lymphocytes ◽  
Significant Difference ◽  
The Mean ◽  
High Doses

Analyses of DNA Damage in the Patient’s Lymphocyte Cells Post-Radiotherapy Radiotherapy given in high doses to kill cancer cells can also induce DNA damage in surrounding normal cells. The radiation dose is divided into smaller doses called fractionation to decrease the effect of radiation on normal tissue. For this reason, it is necessary to monitor the peripheral blood lymphocytes to evaluate the patient's DNA damage. The alkaline comet test is a simple and sensitive technique for detecting DNA instability. This study involved 11 patients who underwent radiotherapy up to 20 Gy, and 11 healthy subjects as controls. This study aims to see how much DNA damage is caused by a 20 Gy fractionated radiation dose in patients with various cancers. The results showed that the mean frequency of damaged cells in patients was 80.54 ± 12.52% with a mean comet tail length of 49.98 ± 12.93 µm. There was a significant difference in both the frequency of damaged cells and the mean value of the comet tail length against the control group (p < 0.001). It was concluded that high doses of radiation can cause DNA damage to peripheral blood lymphocytes. Radioterapi yang diberikan dalam dosis tinggi untuk mematikan sel kanker juga dapat menginduksi kerusakan DNA pada sel normal di sekitarnya. Dosis radiasi dibagi menjadi dosis yang lebih kecil yang disebut fraksinasi untuk menurunkan efek radiasi pada jaringan normal. Untuk itu perlu pemantauan pada limfosit darah tepi untuk mengevaluasi kerusakan DNA pasien. Uji komet alkali merupakan teknik yang sederhana dan sensitif untuk mendeteksi ketidakstabilan DNA. Penelitian ini melibatkan 11 pasien yang menjalani radioterapi hingga 20 Gy, dan 11 subyek sehat sebagai kontrol. Penelitian ini bertujuan untuk melihat seberapa besar kerusakan DNA akibat dosis radiasi fraksinasi 20 Gy pada pasien dengan variasi kanker. Hasil penelitian menunjukkan bahwa rerata frekuensi sel yang rusak pada pasien 80,54 ± 12,52% dengan rerata panjang ekor komet 49,98 ± 12,93 µm terdapat perbedaan nyata baik pada frekuensi sel yang rusak maupun nilai rerata panjang ekor komet terhadap kelompok kontrol (p < 0,001). Penelitian ini menyimpulkan bahwa radiasi dosis tinggi dapat menyebabkan kerusakan DNA sel limfosit darah tepi.

scholarly journals Monitoring of cytogenetic instability by micronuclei assay of both immunocompetent and non-immunocompetent cells in tick-borne encephalitis patients depending on variants of glutathione-S-transferase genes in the genotype

2019 ◽  
Vol 9 (3-4) ◽  
pp. 600-606
Author(s):  
Nikolay Nikolaevich Ilyinskikh ◽  
Ekaterina Nikolaevna Ilyinskikh ◽  
Evgenia Vladimirovna Zamyatina ◽  
Svetoslava Vyacheslavovna Lee
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Micronucleus Assay ◽  
Immunocompetent Cells ◽  
Control Group ◽  
Buccal Cells ◽  
Glutathione S Transferase ◽  
Tick Borne Encephalitis ◽  
Buccal Mucous Membrane ◽  
The One

Aim of this study was to study the dynamics of the frequency of cytokinesis-blocked T-lymphocytes with micronuclei in peripheral blood and the frequency of buccal micronucleated epithelium cells for a period of half a year in patients with acute tick-borne encephalitis, depending on burden of active and inactive variants of glutathione-S-transferase genes (GSTM1 and GSTT1) in the patient's genotype. We carried out micronucleus assay in immunocompetent and non-immunocompetent cells in 54 patients with acute tick-borne encephalitis and 35 healthy persons (control) residing in the Tomsk and Tyumen regions. To analyze the frequency of cytokinesis-blocked micronucleated T-lymphocytes was used venous peripheral blood as material for phytohemagglutinin-stimulated cultures, and to study the frequency of buccal micronucleated cells, samples of the buccal mucous membrane epithelial cells were obtained. To carried out both techniques of micronucleus assay, cytological preparations were prepared, which were stained using the Giemsa or Felgen methods. The material for the study was obtained repeatedly during admission of patients to treatment, and also after 1 week, 1, 3 and 6 months.  Polymerase chain reaction was used to analyze the alleles of the GSTM1 and GSTT1 genes. As a result of this analysis was found a significant increase in the frequency of micronucleated cells in tick-borne encephalitis patients compared with the control group. In addition, the frequency of cytokinesis-blocked micronucleated T-lymphocytes was increased significantly higher than the one of micronucleated buccal cells. The most significant and prolonged increase in the frequency of micronucleated cells was associated with the mutant inactive variants of the genes GSTM1 (0/0) and GSTT1 (0/0). In the patients with burden the inactive forms of these genes, the cytogenetic instability of the cytokinesis-blocked blood T-lymphocytes could persist for up to six months. In case of buccal cells, the frequency of micronucleated cells was close to the one in the control group as early as 1-3 months after a course of treatment. Conclusion. It was found that the most increased and prolonged frequency of cytogenetically instable cells persisted in cytokinesis-blocked T-lymphocytes of peripheral blood of patients with tick-borne encephalitis who were carriers of the genotype with inactive variants of  both GSTM1 (0/0) and GSTT1 (0/0 ) glutathione-S-transferase genes.

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