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

The literature on cell transformation by chemical carcinogens has been critically reviewed. This subject is highly relevant to carcinogenesis in vivo, because the phenotypic changes that are collectively referred to as cell transformation usually involve the acquisition of tumorigenicity on inoculation into suitable rodent hosts. The systems chosen for review fall into 3 categories: cell strains (cells with a limited lifespan); cell lines (cells with an unlimited lifespan); and oncogenic viral-chemical interactions involving cells (Fischer rat embryo cells expressing an endogenous retrovirus, mouse embryo cells expressing the AKR leukemia virus, chemical enhancement of a simian adenovirus, SA7 transformation of Syrian hamster or rat embryo cells). Of the entire literature reviewed, 117 papers have been accepted for data abstraction by pre-defined criteria; these include 41 references to cell strains, 40 in cell lines, and 38 in viral-chemical interactions including cells. Because different systems have been reviewed, it would be meaningless to group all the compounds. The overall summary of the systems is as follows (many compounds have been tested in more than one system and, hence, are duplicated in these totals). (Chart: see text) In general, there is a reasonably good correlation between the results of the cell transformation systems and in vivo carcinogenesis. However, the many deficiencies of the EPA Merged Carcinogen List preclude definitive comparisons. Moreover, a number of 'false negatives' were obtained in systems that did not employ external metabolic activation. Further validation of all systems is required, but it seems very probable that several cell transformation systems will become valuable in assaying (with reasonable time and cost) the carcinogenic potential of environmental chemicals.
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PMID:Cell transformation by chemical agents--a review and analysis of the literature. A report of the U.S. Environmental Protection Agency Gene-Tox Program. 633 91

The modifying effects of butylated hydroxyanisole (BHA), sodium L-ascorbate (SA), phenobarbital (PB) and ethinyl estradiol (EE) were studied by their administration to F344 rats subsequent to initiation with N-methyl-N-nitrosourea (MNU), a wide-spectrum carcinogen inducing tumors in many organs. Rats were initially given 4 doses of MNU (50 mg/kg) intraperitoneally within a 2-week period and then placed on a diet containing BHA (1%), SA (5%), PB (0.05%) or EE (0.001%) for 23 weeks prior to killing. Since the experiment was based on a whole body concept of carcinogenesis, all major organs were examined histologically and histochemically for any preneoplastic lesions. BHA enhanced forestomach and urinary bladder carcinogenesis as did SA also for the urinary bladder, whereas PB enhanced the induction of gamma-glutamyl transpeptidase positive (gamma-GT+) foci in the liver and also the incidence of thyroid carcinoma and forestomach carcinoma. In contrast, EE inhibited the induction of thyroid tumors, malignant lymphoma or leukemia. Thus these compounds, when given after initiation of many organs by a single carcinogen, exert an influence on the site of tumor development by, as yet unknown, organotropic modifying effects.
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PMID:Modification of N-methyl-N-nitrosourea initiated carcinogenesis in the rat by subsequent treatment with antioxidants, phenobarbital and ethinyl estradiol. 649 96

Animal models have strongly suggested that lymphoid leukaemias and malignant lymphomas might have a viral etiology. Following the first report by Ludwig Gross in 1951 of the transmission of mouse leukaemia by cell-free filtrates inoculated into newborn mice and the subsequent identification of many tumour-inducing type-C viruses in animals, attention was focused on the RNA retroviruses. However, it was work in Africa which led to the recognition of Burkitt's lymphoma as an entity and to the discovery of the Epstein-Barr virus. Many refer to this DNA virus as the first recognized human tumour virus. The research that these early studies stimulated has resulted in enormous progress in our understanding of human carcinogenesis and in highly significant advances in therapy. More recently, the first human retrovirus was identified and characterized in the laboratory of Dr Robert Gallo. There is increasing evidence that this virus, isolated from a patient with a T-cell lymphoma, is etiologically associated with a specific type of T-cell neoplasm first described in Japan. Africa may be considered the cradle of geographical pathology and the potential for generating unique information on cancer etiology and cancer control is still enormous. Lymphoid neoplasms are excellent models for the study of human cancer, particularly in Africa, since as tumours of the immune system, their induction and evolution is strongly influenced by those environmental factors, such as infection and nutrition, which have a profound effect on the immune response. In addition, there is good evidence that at least some of the tumours in this group are associated with specific transforming viruses. There is an immediate need to collect accurate, reproducible and comparable data on the incidence and characteristics of the different types of lymphoid neoplasia and on the populations in which they occur in the various African countries. Such data will provide the basis for undertaking simultaneous or subsequent etiological and therapeutic studies. Realistic approaches to these goals are considered and specific studies relating to questions posed by available information discussed.
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PMID:Opportunities for study of lymphoid neoplasia in Africa. 659 1

A considerable amount of concern has been felt recently for the risk of carcinogenesis from x-rays to scoliosis patients. This paper re-evaluates risk in quantitative terms by using some data measured by us and other data recently published in the literature. The risks are considerably smaller than had been estimated earlier. Compared with the natural incidence of cancer in the general population, the cumulative additional risk for scoliosis patients varies from 0.2% for breast carcinoma to 5% for leukemia.
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PMID:A revised estimate of the risk of carcinogenesis from x-rays to scoliosis patients. 670 20

Late side effects of chemotherapy were studied in 51 women who had received at least 300 mg of melphalan for ovarian cancer and had survived for at least three years. Hematologic, statistical, and cytogenetic methods were employed. Six cases of iatrogenic leukemia were found. They appeared to represent a hematologic entity that is fairly difficult to recognize. The risk of iatrogenic leukemia in women who survived for three years or more after melphalan treatment was calculated to be 950 times greater than the leukemia risk in the total female population. The cytogenetic changes were studied with three methods focused on sister chromatid exchange, chromosome aberrations, and DNA damage. The sister chromatid exchange frequency showed a marked increase, but it was corrected within a few months. Chromosome aberrations expressed by chromosome rearrangements were increased in the peripheral lymphocytes and may persist for several years. The frequency of DNA stand breaks was decreased indicating the presence of DNA cross-links. Any of these types of genetic alteration could be the initiating event in carcinogenesis.
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PMID:Late side effects of chemotherapy in ovarian carcinoma: a cytogenetic, hematologic, and statistical study. 707 40

In vitro assay for carcinogenesis, using mammalian cells, provide opportunity for rapid and inexpensive means, compared to in vivo assays, for studying carcinogenesis and for identifying potential carcinogens. These assays must, however, be shown to be reproducible, reliable and able to detect a variety of known carcinogens before they can be recommended for general use. We have, independently, reproduced a transformation assay which utilizes murine leukemia virus-infected rat embryo cells as targets. In the process a new culture, designated 2FR4(50), was generated to replace the F1706 line, of Freeman, which is no longer available. Through careful control of the assay parameters a readily reproducible test has been developed. In 2-4 culture passages after chemical treatment, morphologically transformed foci of cells are observed while no such foci are found in noncarcinogen treated or control cultures. Over 75 compounds have been tested in this assay; 20 of these are detailed here as representative of the chemically diverse types of carcinogens detected.
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PMID:Chemical carcinogenesis in vitro: an improved method for chemical transformation in Rauscher leukemia virus-infected rat embryo cells. 718 72

We have investigated the genotoxicity of two 3'-derivatives of cytidine, 2,3'-O-cyclocytidine (3'-cycloC) and beta-xylocytidine (xyloC), in human leukemia and solid tumor cell lines. Both derivatives were found to be cytotoxic at micromolar concentrations. For example, in the alveolar tumor cell line A549 which was included in all experiments as a reference, drug concentrations required to induce 50% inhibition of cell growth (D50 values) equalled 55 microM for 3'-cycloC and 80 microM for xyloC. Compared with the response of this reference cell line, none of the solid tumor cell lines tested--representing five different malignancies--displayed significant hypersensitivity to these drugs, while the acute lymphoblastic leukemia cell lines proved to be hypersensitive (range of D50 values, 5-13 microM). To gain insight into the modes of cytotoxic action of xyloC and 3'-cycloC, we compared the effect on DNA metabolism of these compounds with that of 1-beta-D-arabinofuranosylcytosine (araC), a potent inhibitor of semi-conservative DNA replication and long-patch excision repair. As seen with araC, the xylo compound strongly inhibited both DNA replicative synthesis and the repair of DNA damage induced by UV light and 60Co gamma-radiation. In gamma-irradiated A549 cells, the extent of repair inhibition by 1 mM xyloC was approximately 40% of that inhibited by araC, and concomitant exposure of the irradiated cultures to xyloC plus araC gave rise to a synergistic response. Since araC was employed at a concentration (0.1 mM) which produced a maximal effect on DNA repair when applied alone, the observed synergistic response implies that the mode of action of xyloC on DNA repair is different from that of araC. In contrast to that observed with xyloC, 3'-cycloC proved to be a very weak inhibitor of DNA replication and repair, strongly suggesting that the genotoxic action of the latter analog may be through a mechanism other than inhibition of DNA synthesis.
Carcinogenesis 1994 Oct
PMID:Comparative genotoxicity of 2,3'-O-cyclocytidine, beta-xylocytidine and 1-beta-D-arabinofuranosylcytosine in human tumor cell lines. 752 96

Recent investigations revealed that the 9p arm and 17q arm of human chromosomes harbour tumour suppressor genes (TSGs) with an important role in multistage carcinogenesis. At the 9p arm is located the p16 (MTS1) TSG and probably others with an effect on various human tumours such as acute lymphoblastic leukaemia, bladder cancer, gliomas, malignant mesotheliomas, melanomas and non-small cell lung carcinomas. In addition, the 17q arm harbours BRCA1 TSG which is responsible for approximately 80% of the familial breast/ovarian cancer cases. In order to investigate the implication of these performed a loss of heterozygosity (LOH) analysis with 10 polymorphic microsatellite markers (three at the 17q arm surrounding the BRCA1 region and seven at the 9p arm). Fourteen of the 17 (82%) tumours exhibited deletions at 9p. The highest incidence of LOH (6/13, 46%) was found for the marker D9S157 at 9p22. One sample exhibited deletion of all the informative markers tested indicating deletion of the complete 9p arm. No homozygous deletions were found. LOH at the 17q arm near the BRCA1 locus was found in 6 (35%) among 17 specimens. The results of this study indicate that allelic deletions at 9p are frequent in the development of laryngeal tumours. The highest incidence of LOH was found for the marker D9S157 which is near, but distinct from the location of p16 (MTS1) tumour suppressor gene, indicating the presence of multiple tumour suppressor genes within this chromosomal region. In addition, BRCA1 TSG is implicated in the development of laryngeal tumours.
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PMID:Loss of heterozygosity at 9p and 17q in human laryngeal tumors. 758 72

The questions of whether and how N-nitroso compounds (NOC) may be inducing cancer in humans are discussed. The principal subjects covered include nitrite-derived alkylating agents that are not NOC, reasons for the wide tissue specificity of carcinogenesis by NOC, the acute toxicity of nitrosamines in humans, mechanisms of in vivo formation of NOC by chemical and bacterial nitrosation in the stomach and via nitric oxide (NO) formation during inflammation, studies on nitrite esters, use of the nitrosoproline test to follow human gastric nitrosation, correlations of nitrate in food and water with in vivo nitrosation and the inhibition of gastric nitrosation by vitamin C and polyphenols. Evidence that specific cancers are caused by NOC is reviewed for cancer of the stomach, esophagus, nasopharynx, urinary bladder in bilharzia and colon. I review the occurrence of nitrosamines in tobacco products, nitrite-cured meat (which might be linked with childhood leukemia and brain cancer) and other foods, and in drugs and industrial situations. Finally, I discuss clues from mutations in ras and p53 genes in human tumors about whether NOC are etiologic agents and draw some general conclusions.
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PMID:Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. 760 May 41

After 30 years of experience with human exposure to dichlorvos (DDVP) in the home, workplace, and sickroom, the U.S. EPA has published its intent to revoke the food additive registration of this cholinesterase-inhibiting insecticide. The basis for the Agency action is the result of the National Toxicology Program (NTP) toxicology and carcinogenesis study of DDVP in rats and mice (NTP Technical Report No. 342, September 1989). In those experiments the NTP considered the result in the female mouse portion of the study to afford unequivocal evidence of carcinogenicity. The NTP considered the interpretations of the male and female rat and the male mouse studies to be less than clear. Despite the NTP interpretation, the EPA considers the male rat data (increased incidence of mononuclear cell leukemia) to be sufficient to warrant the regulatory change. The purpose of this report is to summarize a review of the interpretation of the NTP data and to assess the predictive validity of the results relative to potential human health impact. Critical review of experimental data indicates that the evidence for a carcinogenic effect of DDVP in animals is equivocal. Further, DDVP possess no in vivo mutagenic activity in mammalian assay systems and it bears no significant structural similarity to known carcinogens. Therefore, a weight-of-the-evidence analysis leads to the conclusion that DDVP poses neither mutagenic nor carcinogenic risks to humans exposed under normal conditions of use of foreseeable conditions of misuse.
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PMID:Dichlorvos carcinogenicity: an assessment of the weight of experimental evidence. 772 38


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