A5051551402- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Prenatal Screening and Diagnostics
- Acute Lymphoblastic Leukemia research
- DNA and Nucleic Acid Chemistry
- Molecular Biology Techniques and Applications
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Mentoring and Academic Development
- Virus-based gene therapy research
- Effects and risks of endocrine disrupting chemicals
- Viral-associated cancers and disorders
- Cancer Research and Treatments
- Chromosomal and Genetic Variations
- Coaching Methods and Impact
- Plant Genetic and Mutation Studies
- Microtubule and mitosis dynamics
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Polyomavirus and related diseases
National Cancer Institute
2008-2019
National Institutes of Health
2003-2019
Cancer Genetics (United States)
2013-2018
Center for Cancer Research
2004-2018
National Cancer Institute
2015
National Institute for Occupational Safety and Health
2005-2006
Lovelace Respiratory Research Institute
2003
Bioqual
2002
New York State Department of Health
2000
Wadsworth Center
2000
When given during pregnancy, the drug 3'-azido-2',3'-dideoxythymidine (AZT) substantially reduces maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1). However, AZT has been shown to be carcinogenic in adult mice after lifetime oral administration. In this study, we assessed transplacental tumorigenic and genotoxic effects offspring CD-1 Erythrocebus patas monkeys orally pregnancy.Pregnant were daily doses either 12.5 or 25.0 mg on days 12 through 18 gestation (last 37%...
Although children born to HIV-infected (HIV+) women receiving antiretroviral therapy during pregnancy show virtually no adverse clinical effects at birth, the nucleoside analog drugs are known damage nuclear and mitochondrial DNA. In this study, biomarkers of toxicity genotoxicity have been examined in a well-characterized sample set consisting infants HIV-uninfected (HIV-) mothers (n = 30), HIV- 20) who received either 10) or zidovudine (3'-azido-3'-deoxythymidine [AZT]) 10). DNA from cord...
The nucleoside analog 3'-azido-3'-deoxythymidine (ZDV) has widespread clinical use but also is carcinogenic in newborn mice exposed to the drug utero and becomes incorporated into mouse DNA. This pilot study was designed determine ZDV incorporation human blood cell DNA from adults infants.In this prospective cohort study, peripheral mononuclear cells (PBMC) were obtained 28 non-pregnant 12 pregnant women given therapy, six with no exposure ZDV, who last received > or = 6 months previously....
Drug combinations that include nucleoside reverse transcriptase inhibitors (NRTIs) are remarkably effective in preventing maternal-viral transmission of HIV during pregnancy. However, there may be potential long-term risks for children exposed utero . Examination the genotoxic and mutagenic effects two NRTIs, zidovudine [AZT (3′-azido-3′-deoxythymidine)] didanosine [ddI (2′,3′-dideoxyinosine)], cultured human lymphoblastoid cells revealed multiplicative synergistic enhancement AZT-DNA...
This study was designed to investigate fetal mitochondrial toxicity in Erythrocebus patas monkeys exposed utero zidovudine (AZT) and lamivudine (3TC), taken at term. Pregnant were given a daily dose of 40 mg AZT (86% the human dose, based on body weight), for last 10 weeks (50%) gestation, 24 3TC (84% weight) 4 gestation. At term, found be incorporated into DNA from skeletal muscle, liver, kidney, placenta. By transmission electron microscopy (EM) drug-exposed cardiac muscle cells showed...
The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases.We performed a comprehensive study on collection from women with or benign disease, undergoing annual screening mammography. All had suspicious mammography assessment underwent biopsy. We used indirect immunofluorescence, crithidia assay for anti-dsDNA antibodies, multiple ELISAs extractable nuclear...
Antiretroviral nucleoside analogue drugs are a major constituent of highly active antiretroviral therapy (HAART), the most advanced form treatment for HIV-1 infection. Currently, HAART combinations that include zidovudine (ZDV) and lamivudine (3TC) effective in preventing vertical transmission; children born with no evident adverse clinical effects. However, ZDV is moderately strong transplacental carcinogen mice, potential long-term consequences fetal exposure to remain unknown. To model...
Antiretroviral therapy for the human immunodeficiency virus-1 (HIV-1) typically includes two nucleoside reverse transcriptase inhibitors (NRTIs). 3'-Azido-3'-deoxythymidine (AZT, Zidovudine) plus 2'-deoxy-3'-thiacytidine (3TC, Lamivudine) is a combination that used frequently. The NRTIs are mutagenic analogs become incorporated into DNA and terminate replication. We therefore hypothesized exposure to this class of drug may alter cell cycle parameters. flow cytometry examine in epithelioid...
The genotoxicity of zidovudine (AZT) based treatments was investigated in human H9 lymphoblastoid cells an vitro study and red blood (RBCs) from perinatally exposed HIV-1-infected mothers their infants observational cohort study. Exposure for 24 hr to AZT produced dose-dependent increases Comet assay tail moment (TM) when electrophoresed at pH 13.0, but not 12.1 or 8.0, suggesting that DNA damage via alkali-labile lesions double-stranded strand breaks. TM dose response 13.0 correlated...
Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) thymidine kinase (TK), using cloning assays for assessing effects individual drugs/drug combinations (1) TK6 human lymphoblastoid cells exposed vitro (2) splenic lymphocytes from male CD-1 mice transplacentally days 12-18 gestation. In cells, dose-related increases HPRT TK...
Normal diploid somatic mammalian cell division generates 2 daughter cells as a result of strict and well-controlled mitotic process. However, some defects during the progression that process could generate an unbalanced distribution chromosomes, aneuploidy eventually, malignant phenotype. Previous observations using transgenic mouse model with diminished DNA repair capacity revealed presence nuclear buds (NBs) induced in vitro by nucleoside analog zidovudine (Retrovir®,...
Long-term use of antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs) as therapy for human immunodeficiency virus-1 (HIV-1) infection is limited by mitochondrial toxicity. Here we document pathology during the long-term culture HeLa cells in presence or absence NRTI Zidovudine(R) (AZT, 800 muM) up to 77-passages (p), with samples taken at early (p5-p11), middle (p36 and p37), late (p70-p77) passages. Samples were analyzed changes morphology, (mt)DNA quantity, nuclear gene...
Background. Erythrocebus patas (patas) monkeys were used to model antiretroviral (ARV) drug in human immunodeficiency virus type 1–infected pregnant women.
Summary: In the United States, nucleoside analogue drug 3′-azido-3′deoxythymidine (AZT; also called zidovudine or ZDV) is given to most pregnant women who produce a positive test result for HIV-1. To investigate transplacental distribution and genotoxicity of AZT, near-term rhesus (Macacamulatta) monkeys their fetuses were studied. Four continuously infused with 8 mg AZT/kg body weight 4 hours just prior hysterotomy at term. This short-term AZT exposure resulted in incorporation into DNA...
AZT (3′-azido-2′,3′-dideoxythymidine), the first nucleoside analog approved for treatment of AIDS (acquired immunodeficiency syndrome), induces significant toxic effects in humans exposed to therapeutic doses. As an inhibitor HIV-1 (human virus 1) reverse transcriptase, blocks incorporation nucleotides into host's newly synthesized DNA. Incorporation mammalian DNA as well specific localization drug telomeric DNA, has been previously documented by immunohistochemistry. with other analogs,...