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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of DNA degradation and its clinical applications were examined. When purified lambda phage and extracted liver DNA were fixed in phosphate buffered formaldehyde, the DNA did not degrade, but there was incomplete digestion with endonuclease. Rat liver tissues were fixed under various conditions and DNA extracted. Immediate fixation with buffered formaldehyde at low temperature, or the addition of EDTA to buffered formaldehyde blocked the DNA degradation. Analysis of pulsed field gel electrophoresis also showed that DNA was degraded before extraction. These results suggest that tissue nuclease has an important role in DNA degradation in tissue. Furthermore, formaldehyde fixation at low temperature, which may take time and which decreases slightly the staining capacity, is useful for the extraction of intact DNA. For clinical application, the detection of provirus was examined. Genomic DNA was extracted from a necropsy sample of adult T cell leukaemia fixed in formaldehyde; human T cell leukaemia virus type-I (HTLV-I) provirus was successfully detected by Southern blotting.
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PMID:Fundamental study on the mechanism of DNA degradation in tissues fixed in formaldehyde. 212 Feb 90

Over 30 epidemiologic studies have evaluated cancer risks associated with formaldehyde exposure. Excesses were reported for several sites, leukemia and cancers of the nasal cavities, nasopharynx, lung, and brain generating the greatest interest. The excesses of leukemia and brain and colon cancer found among professionals may not be related to formaldehyde exposure, since similar excesses were not observed among industrial workers. Inconsistencies among and within studies impede assigning formaldehyde a convincing causal role for the excesses of lung cancer found among industrial workers. A causal role for formaldehyde is the most probable for cancers of the nasopharynx and, to a less extent, the nasal cavities. Evidence of exposure-response relationships, the fact that direct contact with formaldehyde may occur at these upper respiratory sites, and the consistency of these findings with experimental studies make this assumption highly probable.
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PMID:Epidemiologic evidence on the relationship between formaldehyde exposure and cancer. 228 88

Evidence indicating that modifications at the 5- and 10-positions of classical folic acid antimetabolites lead to compounds with favorable differential membrane transport in tumor vs. normal proliferative tissue prompted an investigation of 5-alkyl-5-deaza analogues. 2-Amino-4-methyl-3,5-pyridinedicarbonitrile, prepared by hydrogenolysis of its known 6-chloro precursor, was treated with guanidine to give 2,4-diamino-5-methylpyrido[2,3-d]pyrimidine-6-carbonitrile which was converted via the corresponding aldehyde and hydroxymethyl compound to 6-(bromomethyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine. Reductive condensation of the nitrile 8 with diethyl N-(4-amino-benzoyl)-L-glutamate followed by ester hydrolysis gave 5-methyl-5-deazaaminopterin. Treatment of 12 with formaldehyde and Na(CN)BH3 afforded 5-methyl-5-deazamethotrexate, which was also prepared from 15 and dimethyl N-[(4-methylamino)benzoyl]-L-glutamate followed by ester hydrolysis. 5-Methyl-10-ethyl-5-deazaaminopterin was similarly prepared from 15. Biological evaluation of the 5-methyl-5-deaza analogues together with previously reported 5-deazaaminopterin and 5-deazamethotrexate for inhibition of dihydrofolate reductase (DHFR) isolated from L1210 cells and for their effect on cell growth inhibition, transport characteristics, and net accumulation of polyglutamate forms in L1210 cells revealed the analogues to have essentially the same properties as the appropriate parent compound, aminopterin or methotrexate (MTX), except that 20 and 21 were approximately 10 times more growth inhibitory than MTX. In in vivo tests against P388/0 and P388/MTX leukemia in mice, the analogues showed activity comparable to that of MTX, with the more potent 20 producing the same response in the P388/0 test as MTX but at one-fourth the dose; none showed activity against P388/MTX. Hydrolytic deamination of 12 and 20 produced 5-methyl-5-deazafolic acid and 5,10-dimethyl-5-deazafolic acid, respectively. In bacterial studies on the 2-amino-4-oxo analogues, 5-deazafolic acid proved to be a potent inhibitor of Lactobacillus casei DHFR and also the growth of both L. casei ATCC 7469 and Streptococcus faecium ATCC 8043. Its 5-methyl congener 22 is also inhibitory toward L. casei, but its IC50 for growth inhibition is much lower than its IC50 values for inhibition of DHFR or thymidylate synthase from L. casei, suggesting an alternate site of action.
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PMID:Syntheses and antifolate activity of 5-methyl-5-deaza analogues of aminopterin, methotrexate, folic acid, and N10-methylfolic acid. 242 90

Many N1-acyloxymethyl derivatives VI of bis(2,6-dioxopiperazine) I, ICRF-154, were prepared and tested for antitumor activity. The treatment of I with formaldehyde gave a crystalline bis(N1-hydroxymethyl) derivative VII, which was acylated under various conditions to give bis(N1-acyloxymethyl) derivatives VI. Antitumor activity of VI against P388 leukemia in mice was studied. Several bis(N1-acyloxymethyl) compounds such as phenylacetyloxymethyl VI-6, methoxycarbonyloxymethyl VI-41, isobutoxycarbonyloxymethyl VI-44, and furancarboxymethyl VI-38 compounds were found to have potent antitumor activities. On the other hand, water-soluble esters having an amine or a carboxylic acid function in their acyl groups showed rather reduced activity. These bis(N1-acyloxymethyl) derivatives VI were presumably hydrolyzed into the parent bis(2,6-dioxopiperazine) I by nonspecific esterase in the body to exhibit their antitumor activity.
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PMID:Synthesis and antitumor properties of N1-acyloxymethyl derivatives of bis(2,6-dioxopiperazines). 263 42

The gp70 envelope glycoproteins of ecotropic murine leukemia viruses bind to receptors that occur only on mouse and rat cells and on interspecies hybrid cells that contain mouse chromosome 5. A substantial fraction of the gp70 that was bound specifically by these criteria remained undegraded and accessible to extracellular labeling reagents for many hours. Accordingly, cells with ecotropic receptors could be labeled specifically. As seen by immunofluorescence microscopy, the gp70-receptor complexes were uniformly dispersed on mouse fibroblast plasma membranes. These complexes were mobile, and they aggregated into patches when crosslinked by antibodies at 37 degrees, but not when membrane lipid fluidity was frozen at 0 degrees. Ecotropic receptors still bound gp70 specifically after cells were fixed with 3.7% formaldehyde, but these receptors could not be patched, indicating that they were nondiffusible. Viable cells slowly endocytosed gp70-receptor complexes at 37 degrees (approximate half-life 5-7 hr) and the gp70 was then proteolytically degraded in lysosomes. In the presence of 20 microM chloroquine, a lysosomal inhibitor, undegraded gp70 was seen to slowly accumulate in these intracellular organelles. These results suggest that ecotropic receptors mediate a slow internalization of attached ligand. Long-lived binding of gp70 onto surfaces of uninfected cells may explain important features of viral-induced leukemia, the host immune response, and immunosuppression.
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PMID:Cell surface receptors for ecotropic murine retroviruses: mobile membrane proteins that mediate binding and slow endocytosis of the viral envelope glycoprotein. 266 24

Sixteen 2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolines (I) were synthesized by two different methods. 2-Nitro-5-chloro-benzonitrile was treated with the appropriate N-methyl-substituted benzylamines and I was formed after reduction and cyclization. Another method was reductive methylation, i.e., 2,4-diamino-6-substituted benzylaminoquinazolines reacted with formaldehyde and sodium cyanoborohydride at pH 6.3. Suppressive therapeutic tests in mice infected with Plasmodium berghei showed that four (I6,7,10,16) out of these compounds suppressed all the parasites when administered orally at the dose of 5 mg/kg and produced more than 99% suppression at 2.5 mg/kg. Eight compounds (I1,2,4,5,8-10,15) were found to have antitumor effects against Leukemia cells in culture comparable with or superior to those of the positive control methotrexate.
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PMID:[Synthesis and antimalarial as well as antitumor activities of 2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolines]. 267 93

A method using flow cytometry and fluorescent in situ hybridization (ISH) to detect RNA in cells is described. L1210 murine leukemia cells were fixed with 1% formaldehyde in HEPES buffered Hank's balanced salt solution (HH) followed by 70% ethanol. Endogenous RNAses were blocked by diethylpyrocarbonate treatment. Single-stranded sense and antisense RNA probes, labeled with biotin-11-UTP, were transcribed from a 2.1 kb 28S ribosomal RNA (rRNA) gene fragment subcloned into the pGEM2 plasmid. For good results, it was essential that the probes were degraded to 100-150 nucleotides before use. Hybridization was performed at 45 degrees C in 50% formamide, 5 x SSC, 0.5% SDS. Hybrids were detected with streptavidin-FITC by flow cytometry. Antisense rRNA probe signal was 100 times higher than the background. The hybrids were largely resistant to RNAse and melted at high temperature. The sense probe also gave a signal (5 times background), which was not RNAse resistant and was attributed to the presence of internal inverted repeats in the ribosomal RNA. When sufficient background reduction can be achieved, it is expected that as few as ten mRNA molecules per cell can be detected with the fluorescent in situ hybridization method.
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PMID:Flow cytometric detection of ribosomal RNA in suspended cells by fluorescent in situ hybridization. 320 17

In order to assess the possible human carcinogenicity of formaldehyde we conducted a retrospective cohort mortality study of workers exposed for at least three months to formaldehyde in three garment facilities which produced permanent press garments. A total of 11,030 workers contributing 188,025 person-years were included in the study. Vital status was successfully ascertained through 1982 for over 96% of the cohort. The average (TWA) formaldehyde exposure at the three plants monitored in 1981 and 1984 by NIOSH was 0.15 ppm but past exposures may have been substantially higher. In general, mortality from nonmalignant causes was less than expected. A statistically significant excess in mortality from cancers of the buccal cavity (SMR = 343) and connective tissue (SMR = 364) was observed. Statistically nonsignificant excesses in mortality were observed for cancers of the trachea, bronchus and lung (SMR = 114), pharynx (SMR = 112), bladder (SMR = 145), leukemia and aleukemia (SMR = 113), and other lymphopoietic neoplasms (SMR = 170). Mortality from cancers of the trachea, bronchus and lung was inversely related to duration of exposure and latency. In contrast, mortality from cancers of the buccal cavity, leukemias, and other lymphopoietic neoplasms increased with duration of formaldehyde exposure and/or latency. These neoplasms also were found to be highest among workers first exposed during a time period of high potential formaldehyde exposures in this industry (1955-1962). However, it should be recognized that these findings are based on relatively small numbers and that confounding by other factors may still exist. The results from this investigation, although far from conclusive, do provide evidence of a possible relationship between formaldehyde exposure and the development of upper respiratory cancers (buccal), leukemias, and other lymphopoietic neoplasms in humans.
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PMID:A retrospective cohort mortality study of workers exposed to formaldehyde in the garment industry. 338 62

A historical cohort study evaluated the mortality experience of 26,561 workers employed in 10 formaldehyde-producing or -using facilities. Approximately 600,000 person-years of follow-up accrued as workers were followed to January 1, 1980. Estimates of historical exposure to formaldehyde by job were developed by project industrial hygienists using monitoring data available from participating plants, comments from long-term workers, and comprehensive monitoring data specifically collected for this study. Mortality from all causes combined was about as expected [standardized mortality ratio (SMR) = 96] based on mortality rates of the general U.S. population. Significantly fewer deaths occurred from infective and parasitic diseases (SMR = 51) and from accidents (SMR = 72) than expected. Cancer overall was not related to formaldehyde exposure. Workers exposed to formaldehyde had slight excesses for Hodgkin's disease and cancers of the lung and prostate gland, but these excesses were not consistently related to duration of or average, cumulative, or peak formaldehyde exposure levels. Recent animal studies found nasal cancer among rats exposed to formaldehyde, but no excess of this tumor occurred in this study. Mortality from brain cancer and leukemia among these industrial workers was not excessive in contrast to reported excesses among professional groups (e.g., anatomists, embalmers, and pathologists) with exposure to formaldehyde. Although there was a deficit for cancer of the buccal cavity and pharynx, mortality from certain subsites, i.e., the nasopharynx and oropharynx, was elevated. These subsites did not, however, show a consistently rising risk with level of exposure. These data provide little evidence that mortality from cancer is associated with formaldehyde exposure at levels experienced by workers in this study.
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PMID:Mortality among industrial workers exposed to formaldehyde. 793 14

Anatomists are exposed to a wide range of solvents, stains, and preservatives used to prepare biologic specimens. One fixative, formaldehyde, has recently been shown to cause nasal cancer in laboratory rodents. A retrospective cohort study was conducted to assess whether anatomists have an increased risk of mortality from cancer, particularly from cancers of the respiratory tract. The cohort included 2,317 men who joined the American Association of Anatomists between 1888 and 1969 and who were living in the United States when they joined this association. Standardized mortality ratios were 0.3 for lung cancer [95% confidence interval (CI) = 0.1-0.5], 1.5 for leukemia (95% CI = 0.7-2.7), and 2.7 for brain cancer (95% CI = 1.3-5.0) when mortality rates for U.S. white males, available for 1925-79, were used as the referent. When rates for male members of the American Psychiatric Association, available for 1900-69, were used as the referent, standardized mortality ratios were 0.5 for lung cancer (95% CI = 0.2-1.1) and 6.0 for brain cancer (95% CI = 2.3-15.6). Each of the 10 anatomists who died of brain cancer between 1925 and 1979 had a neuroglial cell tumor (either astrocytoma or glioblastoma). The increased risk for leukemia was limited to the myeloid cell type. An etiologic agent associated with these increased risks was not identified.
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PMID:Brain cancer and other causes of death in anatomists. 346 14


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