Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Procarbazine (PCZ) is an antineoplastic agent useful in the treatment of Hodgkin's disease, brain tumors, and chronic leukemia. PCZ is dysmorphogenic to developing embryos exposed in vivo or cultured in the serum of PCZ-treated rats. However, embryos directly cultured with PCZ (up to 400 micrograms/ml) or PCZ plus S-9 liver fractions are unaffected. Since intact liver cells provide several advantages over hepatic subcellular fractions for in vitro bioactivation, we exposed rat embryos to PCZ in an embryo/hepatocyte co-culture system. Gestation day (GD) 9.5 rat embryos exposed to 0, 200, 300, or 400 micrograms PCZ/ml in the presence of untreated or phenobarbital induced male rat hepatocytes failed to display toxicity. However, in a companion study GD 9.5 rat embryos cultured in the serum from PCZ-treated rats exhibited developmental deficiencies. Studies have shown that the formation of toxic metabolites can result from glutathione (GSH) conjugation of toxicants in the liver. Therefore, in a second set of experiments, rat embryos were cultured in serum from rats pretreated with two GSH depleters (phorone and buthionine sulfoximine) and subsequently dosed with PCZ. Effects on development were enhanced when embryos were cultured in the serum from PCZ-treated/GSH depleted rats. These data indicate that PCZ requires in vivo activation to be dysmorphogenic and further suggest that the metabolite(s) responsible for procarbazine embryo-toxicity are formed readily under conditions of low GSH levels. This argues against a glutathione conjugate as the ultimate toxicant.
Teratog Carcinog Mutagen 1995
PMID:Profile of procarbazine-induced embryotoxicity in an embryo hepatocyte co-culture system and after in utero glutathione depletion. 760 90

In vivo measurement of human somatic mutations may be a valuable biodosimeter of exposure to carcinogens and of cancer risk. We have surveyed translocations at the bcl2 locus in B lymphocytes, and mutations at hprt in T lymphocytes, in 120 individuals with varying exposure to radon and cigarette smoke. bcl2 t(14:18) translocation is the commonest chromosomal alteration observed in non-Hodgkins lymphoma (NHL). We observed a significantly larger range of bcl2 translocation frequency (range: 0-372 x 10(-6), median: 1.9 x 10(-6)) than of hprt mutation frequency (range: 0-76.4 x 10(-6), median: 11.1 x 10(-6)), which is likely the result of clonal proliferation of deathless B cell mutants. We observed that the frequencies of these two distinct lymphocytic mutations are significantly correlated. Although some of the correlated variation is explained by age, a significant correlation of bcl2 mutagenesis persists after age adjustment. Correlated mutagenesis at distinct loci in distinct cell types could be explained by the existence of a mutator phenotype or by variation in exposure to environmental mutagens. NHL is commoner in men than in women, and our data indicate a trend toward higher bcl2 mutagenesis in males than females. There is mounting epidemiological evidence for a worldwide increase in NHL, which may have an environmental basis; molecular epidemiological analysis of bcl2 mutagenesis in exposed populations might be especially relevant to the identification of putative environmental causes. Given the relative ease of the bcl2 assay versus the hprt assay, and the consistency with which data are reproduced from laboratory to laboratory, it is likely that the bcl2 assay will be soon added to the array of assays used in human mutational surveillance.
Environ Mol Mutagen 1997
PMID:Correlated mutagenesis of bcl2 and hprt loci in blood lymphocytes. 902 Mar 5

For DNA strand break analysis in human white blood cells, usually metrizoate-Ficoll centrifugation is used to isolate mononuclear cells. This procedure is time-consuming and requires at least 20 ml of blood per sample. Therefore, we developed a technique which does not require isolation of white blood cells prior to DNA strand break analysis by alkaline elution (direct method). The sensitivity of this new technique was compared to that of the standard method, which includes isolation of mononuclear blood cells. A statistically significant increase in sensitivity was observed using the direct method. After in vitro gamma-irradiation of venous blood, an increase in the elution rate of 7.7 x 10(-3) hr(-1)/Gy was detected if mononuclear blood cells were isolated compared to 10.5 x 10(-3) hr(-1)/Gy with the new technique (P < 0.05). Incubation of venous blood with ethylene oxide for 1 hr caused an increase in the elution rate of 5.8 x 10(-3) hr(-1)/mM ethylene oxide for the standard and 12 x 10(-3) h(-1)/mM for the direct method (P < 0.05). DNA single-strand breaks were detected in blood cells of 10 persons without any apparent genotoxic exposure. A mean normalized elution rate of 1.30 +/- 0.38 (95% confidence interval) was detected in isolated mononuclear blood cells, and a similar mean normalized elution rate of 1.41 +/- 0.50 was obtained using the direct method. The difference was not statistically significant. Five patients treated with a combination chemotherapy consisting of cyclophosphamide (750 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.), vincristine (1.4 mg/m2 i.v.), and prednisolone (100 mg/m2 p.o.) for non-Hodgkin's disease were analyzed for DNA single-strand breaks before and 16-18 hr after the application of chemotherapy. Increases in mean elution rate of 68% and 116% were detected using the standard and the direct methods, respectively. For the direct method, only 3 ml of venous blood were sufficient for analysis of one sample, compared to 25 ml needed if mononuclear cells were isolated, and about 4 hr of work per assay can be saved.
Environ Mol Mutagen 1997
PMID:Analysis of DNA single-strand breaks in human venous blood: a technique which does not require isolation of white blood cells. 902 Mar 8

To determine whether the measurement of repeat number mutations at a minisatellite locus could detect human germline mutations induced by chemotherapy, we performed a longitudinal study of the mutation frequencies in sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reaction on small pools of DNA equivalent to 100 sperm and Southern blotting were used to screen at least 7900 sperm in each sample to quantify the mutation frequency at the minisatellite MS205 locus. Pretreatment and posttreatment semen samples were obtained at least 2 months after completion of therapy from 4 patients treated with a regimen (Novantrone, Oncovin, vinblastine and prednisone [NOVP]) that lacks alkylating agents and from three patients treated with regimens (Cytoxan, vinblastine, procarbazine and prednisone/Adriamycin, bleomycin, dacarbazine, lomustine, and prednisone [CVPP/ABDIC] or mechlorethamine, Oncovin, procarbazine and prednisone [MOPP]) containing alkylating agents. There were no effects of NOVP or CVPP/ABDIC on the mutation frequencies. In the 1 patient treated with MOPP, the treatment with the highest dose of gonadotoxic alkylating agents, there was a statistically significant increase in mutation frequency from 0.79% pretreatment to 1.14% posttreatment, indicating induction of mutations in stem spermatogonia. During-treatment semen samples obtained from 2 patients treated with ABVD, which does not contain gonadotoxic alkylating agents, and 1 with NOVP also did not show any increases above the baseline mutation frequencies, indicating no increase in the minisatellite mutation frequency in spermatocytes. Thus, measurement of repeat number changes at minisatellite MS205 appears to be able to detect induced germline mutations in human sperm. However, most chemotherapy regimens do not significantly increase this class of mutations.
Environ Mol Mutagen 2000
PMID:Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy. 1101 12

The link between exposure to environmental mutagens and the development of cancer is well established. Yet there is a paucity of data on the relationship between gene-environment interactions and the mechanisms associated with the somatic mutational events involved with malignant transformation, especially in children. To gain insight into somatic mutational mechanisms in children who develop cancer, we determined the background mutant frequency (Mf) in the hypoxanthine phosphoribosyl transferase (HPRT) reporter gene of peripheral blood lymphocytes from pediatric cancer patients at the time of diagnosis and prior to therapeutic intervention. We studied 23 children with hematologic malignancies and 31 children with solid tumors prior to initial therapeutic intervention. Children with solid tumors, specifically sarcomas, and Hodgkin's disease were significantly older and had elevated HPRT Mfs (6.1 x 10(-6) and 3.7 x 10(-6), respectively) at the time of diagnosis, compared to normal controls (2.3 x 10(-6)) and other pediatric tumor groups including children with acute lymphocytic leukemia and non-Hodgkin's lymphoma (ALL/NHL, 1.7 x 10(-6)), central nervous system tumors (CNS, 3.6 x 10(-6)), and neuroblastoma (1.9 x 10(-6)). Of importance is that the significant differences observed in HPRT Mfs between these groups no longer existed after correcting for the effects of age. These data demonstrate that in children who develop cancer there appears to be no significant increase in background HPRT Mf that would indicate significant exposure to genotoxic chemicals or an underlying DNA repair defect resulting in genomic instability. In addition, these data demonstrate the importance of correcting for the effect of age when comparing the frequency of somatic mutations in children and should provide baseline data for future longitudinal biomonitoring studies on the genetic effects of chemotherapy in children treated for cancer.
Environ Mol Mutagen 2003
PMID:Comparative analysis of HPRT mutant frequency in children with cancer. 1287 12

X-radiation remains the treatment of choice in most cases of leukemia and lymphoma, but new agents are playing an increasing role in therapy. Radioactive phosphorus does not produce radiation sickness and results with it are comparable to those of x-ray therapy in chronic leukemia. Urethane and nitrogen mustard may produce remissions in patients with chronic leukemia who have become resistant to radiation. Triethylene melamine may be administered orally with nitrogen mustard-like effects and is undergoing further trial. Aminopterin, ACTH and cortisone often cause short remissions in acute leukemia. Urethane is the best treatment available for multiple myeloma. Polycythemia vera is well controlled by radioactive phosphorus combined with venesection. Nitrogen mustard is often effective and triethylene melamine shows promise in Hodgkin's disease. Antianemic substances such as iron and liver extract are of no value in the treatment of anemia caused by leukemia, lymphoma and myeloma.
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PMID:New therapy for leukemia, polycythemia, and lymphoma. 1301 1

Trisethylene-imino-s-triazine (triethylene melamine or TEM) produced minimal effects in inhibiting transplantable lymphoma and mammary adenocarcinoma in mice. In strain A mice, injection of the compound induced pulmonary tumors.TEM was tried on 32 patients with neoplastic disease, including nine patients with Hodgkin's disease and five with lymphosarcoma and lymphatic leukemia. The therapeutic and toxic effects were similar to those observed with nitrogen mustard (HN2). Satisfactory remissions of up to three months were observed in Hodgkin's disease and lymphosarcoma following parenteral administration of TEM. It is the authors' impression that the remissions obtained with TEM were not as complete and did not last as long as those obtained with HN2.TEM is effective by the oral route as well as parenterally, and produces much less emetic reaction than HN2. On the other hand, the chemotherapeutic range is narrower than that of HN2. Patients who do not respond to HN2 show no response to TEM.TEM is a drug of some clinical usefulness in the same conditions and with the same general limitations and toxic effects as HN2. The ease of administration of TEM increases its hazards, and close clinical and hematologic observations are essential on patients receiving the agent.
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PMID:Trisethylene-imino-s-triazine (triethylene melamine or TEM) in the treatment of neoplastic diseases. 1484 18

Epidemiological studies show that benzene exposure is associated with an increased incidence of leukemia and perhaps lymphoma. Chromosomal rearrangements are common in these hematopoietic diseases. Translocation t(14;18), the long-arm deletion of chromosome 6 [del(6q)], and trisomy 12 are frequently observed in lymphoma patients. Rearrangements of the MLL gene located on chromosome 11q23, such as t(4;11) and t(6;11), are common in therapy-related leukemias resulting from treatment with topoisomerase II inhibiting drugs. To examine numerical and structural changes in these chromosomes (2, 4, 6, 11, 12, 14, and 18), fluorescence in situ hybridization (FISH) was employed on metaphase spreads from workers exposed to benzene (n = 43) and matched controls (n = 44) from Shanghai, China. Aneuploidy (both monosomy and trisomy) of all seven chromosomes was increased by benzene exposure. Benzene also induced del(6q) in a dose-dependent manner (P(trend) = 0.0002). Interestingly, translocations between chromosomes 14 and 18, t(14;18), known to be associated with follicular non-Hodgkin lymphoma, were increased in the highly exposed workers (P < 0.001). On the other hand, translocations between chromosome 11 and other partner chromosomes that are found in therapy-induced leukemias were not increased. These data add weight to the notion that benzene can induce t(14;18) and del(6q) found in lymphoma, but do not support the idea that benzene induces t(4;11) or t(6;11). However, they do not rule out the possibility that other rearrangements of the MLL gene at chromosome 11q23 may be induced by benzene.
Environ Mol Mutagen 2007 Jul
PMID:Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers. 1758 86

The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR)(CT) = 0.60, 95% confidence interval (CI) = 0.42-0.87, P(trend) = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR(CT) = 0.39, 95% CI = 0.20-0.73; P(trend) = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.
Environ Mol Mutagen 2012 Mar
PMID:Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma. 2217 86

Advances in cancer treatment have led to an increase in patient survival. However, exposure to genotoxic chemotherapeutic agents and ionizing radiation may induce persistent genetic damage in cancer survivors. In this study, we detected genomic instability in chromosomes of peripheral blood lymphocytes from Hodgkin lymphoma patients, 2-17 years after MOPP (nitrogen mustard, Oncovin, procarbazine, and prednisone) chemotherapy with or without radiotherapy. Samples were obtained from 11 healthy individuals, 5 pretreatment patients, and 20 posttreatment patients. Cytogenetic analysis with GTG banding was performed on 1,000 lymphocyte metaphases per donor to identify genomic instability, including numerical and structural chromosomal aberrations, at a resolution of 10 Mb across the entire genome. Our results showed that anticancer treatment did not induce significant differences in the frequency of aneuploidy among the three study groups. However, 1 of the 11 healthy individuals, and 13 of the 20 posttreatment patients had a high frequency of chromosomal breaks and gross chromosomal rearrangements. The types of aberrations observed were random and complex, consistent with persistent genomic instability that was induced by cancer treatment. Clonal expansion of cells with chromosomal lesions was observed in one posttreatment patient only. These findings show that anticancer treatments induce persistent genomic instability, but not aneuploidy. Chemotherapy may affect genes with a role in DNA damage surveillance or repair, which in turn allows the accumulation of nontargeted structural chromosomal damage in future generations of cells. This genomic instability may facilitate the development of second malignancies in Hodgkin lymphoma survivors.
Environ Mol Mutagen 2012 May
PMID:Persistent genomic instability in peripheral blood lymphocytes from Hodgkin lymphoma survivors. 2243 55


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