Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine hybrids (C57BL/6J X C3Hf)F1 (B6C3) and (C57BL/6J X BALB/c)F1 (B6C), which have a high and low spontaneous and induced incidence of hepatocellular tumors, respectively, were treated with a single dose of NDEA at 1 week of age followed by TCPOBOP, a phenobarbital-like promoter of liver carcinogenesis, or by vehicle, and sacrificed at 30 weeks of age. The frequency per liver of hepatocellular nodules was similar in the two hybrids. However, in male mice the mean volume of nodules was about 10-fold greater in B6C3 than in B6C mice receiving NDEA followed by vehicle, and the treatment with TCPOBOP after NDEA stimulated nodule growth, with a much greater response in B6C3 mice. In female mice no differences in the mean volume of nodules were seen between hybrids after NDEA and vehicle, whereas upon NDEA and TCPOBOP treatment the mean volume of nodules was 25-fold greater in B6C3 than in B6C females. In addition, a few hepatocellular adenomas and carcinomas were observed, mostly in animals treated with NDEA and TCPOBOP, and they were 3-fold more numerous among B6C3 than B6C mice. TCPOBOP alone induced the same biochemical and hyperplastic effects in the liver of both hybrids. Using DNA probes homologous to Moloney murine leukemia virus, intracisternal A particle and virus-like 30S sequences, no correlation was apparent between the expression of any of these endogenous retroviral families and the strain susceptibility to hepatocarcinogenesis. We hypothesize that the different susceptibility to hepatocarcinogenesis between B6C3 and B6C mice is related to a higher growth rate of B6C3 than B6C initiated liver cells.
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PMID:Genetic susceptibility to murine hepatocarcinogenesis is associated with high growth rate of NDEA-initiated hepatocytes. 358 13

Numerous studies have reported a positive relationship between dietary fat and chemically induced tumor incidence. The results of the 2-year carcinogenesis bioassay used by the National Toxicology Program (NTP), in which test compounds were administered to rodents by corn oil gavage, provide an opportunity to compare the effects of fat on chemically induced and naturally occurring tumors. Oil gavage increases the fat intake about threefold, equivalent to a 15% fat diet. Only 2 oil gavage effects were observed in the NTP carcinogenesis bioassay. First, pancreatic hyperplasia was increased from 2.6% in untreated controls to 12.6% in male Fischer 344/N vehicle control rats; however, this sporadic and weak effect did not influence the outcome of carcinogenesis bioassays. Second, leukemia/lymphoma incidence was about 50% lower in male vehicle controls than in the untreated control rats; in contrast, this strong effect increased survival by 8-10%. Therefore, oil gavage had an apparent protective effect in male Fischer 344/N rats. The absence of growth enhancement for the relatively high background level of tumors in oil gavage-treated rats was remarkable and is inconsistent with observations in rat mammary tumor model studies. Because it is impossible to extrapolate the enhancing effect of a high fat diet on tumor growth from rodent tumor models to the NTP carcinogenesis bioassay, great caution should be used in extrapolating from rodent tumor model studies to the human situation.
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PMID:Oil gavage effects on tumor incidence in the National Toxicology Program's 2-year carcinogenesis bioassay. 359 39

It has been reported that most human carcinomas result from exposure to the carcinogens present in certain foods, products of cigarette smoking and the general environment. A number of chemicals have already been isolated and tested for potential carcinogenesis in animals, and we report on the following aspects of chemical carcinogenesis. A series of new mutagenic heterocyclic amines have been isolated from pyrolysates of amino acids and proteins, and from cooked foods such as the charred parts of broiled fish and meat. Among these heterocyclic amines, nine compounds have been studied in long-term animal experiments, all of which were shown to cause carcinomas in mice. Some chemicals were also proved to be carcinogenic in rats. Because of their eating habits, people may simultaneously ingest mutagens and carcinogens, both of which have been found in certain cooked foods. Nitrosatable precursors of mutagens and tumor promoters have also been discovered in food--a finding of great importance in this particular context. Thus, it would appear that people are ingesting carcinogens, precursors of mutagens, tumor promoters, and tumor inhibitors, simultaneously. Commonly encountered human pathological conditions, such as viral and bacterial infections, non-infections inflammatory diseases, nutritional disorders, hormonal or homeostatic disturbances, gall and/or kidney stones, and benign proliferative disorders may be shown to be precursors for the development of future cancers. In most cases, however, the scientific evidence to support this theory has not been completely evaluated, but the existence of such pathological conditions should be taken into consideration whenever the development of a cancer is being studied. The division which at one time existed between basic cancer research and the clinical investigation of the disease has begun to disappear. The importance of clinical investigation and its use in the prevention of disease has been demonstrated, for example, in studies of adult human T-cell leukemia.
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PMID:[Improving cancer treatment, from the standpoint of basic cancer research]. 359 86

The effect of the chronic feeding of methionine or choline on liver tumor promotion by phenobarbital (PhB) or 1,1 bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) was studied in rats receiving an initiating dose of diethylnitrosamine (DEN). Male weanling rats were injected i.p. with DEN (200 mg/kg body wt). Control rats were injected with saline. Five days after the injection, the rats were placed on different diets containing 0.05% PhB or 0.05% DDT with or without added 1.5% DL-methionine or 1.0% choline chloride. Each diet was administered for 72 weeks, when the animals were placed on the unsupplemented chow diet for an additional 30 weeks. Rats treated with DEN and then fed PhB or DDT developed an 85-100% incidence of hepatocellular carcinomas (HCCs). Single injection of DEN alone produced a 60% incidence of HCCs. Dietary feeding of methionine and choline either alone or in combination with PhB or DDT did not have any significant effect on the incidence of HCC's. Liver tumor formation was negligible in uninitiated rats. Lung metastases developed in 42% and 46% of the DEN + PhB- and DEN + DDT-treated groups, respectively. Supplementation of methionine in the diet lowered the incidence of lung metastases to 14% in the DEN + PhB-treated rats and to 19% in DEN + DDT-treated rats. Choline was not effective in inhibiting the development of lung metastases in either case. The injection of DEN alone produced a 54% incidence of lung tumors. PhB and DDT feeding lowered the DEN-induced lung tumor incidence to 23% and 14% respectively. Further, when the data from different diet groups were combined it was found that single injection of DEN also doubled the incidence of leukemia normally seen in F344 rats. The present report constitutes the first evidence that a single injection of DEN induces lung tumors and enhances the incidence of leukemia in rats.
Carcinogenesis 1986 Apr
PMID:Effect of methionine and choline on liver tumor promotion by phenobarbital and DDT in diethylnitrosamine-initiated rats. 369 86

Normal rat kidney (NRK) cell were found to be resistant to neoplastic transformation by diverse carcinogenic chemicals. To study chemical-retroviral co-carcinogenesis in this cells they were infected with a low multiplicity of Moloney murine leukemia virus (M-MLV). Using a single cell cloning procedure, a virus-producing clone was isolated from the infected cells, which was shown to carry only one integrated M-MLV provirus per cell. It was found that this single provirus was sufficient to render the clone susceptible to transformation by 3-methylcholanthrene (3-MC). However this clone responded differently to the carcinogen at different passages after infection. When exposed to 3-MC at a low passage postinfection (passage 5), cell transformation was evident only after 11 subsequent subcultures. On the other hand when it was chemically treated at a high passage postinfection (passage 29), cell transformation could clearly be detected already at the next subculture after the chemical treatment. It is suggested that an M-MLV-mediated cumulative effect is necessary to complement the action of the carcinogen in order to complete the carcinogenic process in these cells. This cumulative viral effect appeared to be associated with a change in the control of the virus expression, since 3-MC was found to stimulate virus replication in this clone also only at the high passage postinfection. Indeed virus release by cells of isolated transformed foci, produced by the chemical-M-MLV co-carcinogenesis, was extremely higher than by untransformed cells.
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PMID:Effect of Moloney murine leukemia virus on the carcinogenicity of 3-methylcholanthrene in normal rat kidney cells. 372 25

To determine whether B or T lymphoid malignancies could be induced following the exposure of lymphoid cells within different lymphoid organs to a potential chemical carcinogen, 3-methylcholanthrene (3-MC) was directly injected into surgically exposed Peyer's patches (PP), mesenteric lymph nodes (MLN), axillary lymph nodes (ALN) or spleens (SP) of Copenhagen rats. A high incidence of lymphoproliferative disorders was observed within rats which received 3-MC injections into the PP, but not in MLN, ALN or SP injected groups of rats. In addition to the PP environment, the dose of 3-MC and exposure to pristane were important factors in the induction of T versus B cell disorders. Whereas the B cell diseases were observed in pristane-treated rats which also received PP injections of low doses (5 or 50 micrograms) of 3-MC, in animals receiving a higher dose (500 micrograms) a much higher incidence of T cell disorders was detected. The observed lymphoproliferative diseases were categorized as B lymphocytic leukemias, B lymphomas or thymic lymphomas on the basis of histological examination of the tissues, white blood cell numbers and differentials, and the morphological and phenotypic characteristics of cell isolates. Abnormal DNA staining characteristics, increased soft agar cloning frequencies and metastasis of the leukemia or tumor cells indicated that malignant cells were associated with the proliferative diseases. Collectively the data indicate that primary lymphoid malignancies of either B or T cell origins may be preferentially and reproducibly induced by localizing low or high doses respectively, of 3-MC within the PP of rats exposed to pristane. These results suggest that PP may have a possible role in the carcinogenesis of lymphocytes following the exposure to chemical carcinogens via the gastrointestinal tract.
Carcinogenesis 1986 Aug
PMID:The role of the Peyer's patch in carcinogenesis. II. 3-Methylcholanthrene-induced lymphoid malignancies in rat Peyer's patches. 373 80

Control data on F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mammary tumor virus-free mice from the National Toxicology Program (NTP) were examined to determine if animals receiving corn oil by gavage showed tumor incidences that differed from those of untreated control animals. Analyses of these data were adjusted for interlaboratory variability, time-related trends, and supplier effects. Two biologically significant effects were found: Male F344/N control rats receiving corn oil by gavage showed a higher (P less than .05) incidence of pancreatic acinar cell adenoma and a lower (P less than .001) incidence of leukemia (primarily mononuclear cell leukemia) than did the corresponding untreated controls. The increased incidences of pancreatic acinar cell adenoma seen in male rats administered corn oil by gavage were associated with elevated body weights observed in these animals relative to untreated controls. Female F344 rats and male and female B6C3F1 mice showed little or no evidence of a difference in tumor incidence between corn oil gavage-treated and untreated controls. A review of nearly 300 carcinogenesis studies done by the National Cancer Institute (NCI) and the NTP revealed that there were no corn oil gavage studies in which increased incidences of pancreatic acinar cell tumors or leukemia in male F344/N rats were the sole evidence of the carcinogenicity of a test chemical. Thus use of corn oil appears to have little impact on the interpretation of NCI-NTP carcinogenicity studies.
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PMID:Neoplasms observed in untreated and corn oil gavage control groups of F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mice. 386 95

The occurrence of metachronous malignancies has long been a phenomenon of interest to physicians. The problem of treatment-related malignancies has added to that interest and has contributed to the understanding of carcinogenesis. Prolonged survival of patients with previously lethal diseases is now allowing the expression of long-term toxicities of the intensive therapies being used in many disease settings. Although the oncogenic potential of the various alkylating agents may not be equivalent, they have all been implicated as causing cancer in man. Procarbazine also appears to be highly carcinogenic in man. The intensity of treatment (duration and total dose) is a significant factor in the carcinogenesis of these agents. The dose-response relationship between radiation and cancer induction is less clear, but most believe that increasing radiation exposure increases the risk of cancer in a linear fashion. The combination of intensive chemotherapy and intensive radiotherapy yields the greatest risk for treatment-related hematologic and solid malignancies. To replace effective therapy with less carcinogenic therapy of unproved effectiveness would be difficult since survival curves have not been significantly affected by the evolution of treatment-related cancers. Whether that will hold true for the adjuvant use of intensive therapy remains to be seen. Where feasible, the design of such adjuvant trials should keep the dose-response relationship in mind. If the virtual absence of metachronous leukemia in Hodgkin's disease patients treated with ABVD holds true over time, the search for noncarcinogenic combination therapy will be well worth the effort. Therapeutic options in cancer treatment currently are few, and the benefits of potentially carcinogenic chemotherapy and radiotherapy continue to outweigh the risks.
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PMID:Second cancers following antineoplastic therapy. 388 36

Cancer induction is generally considered to be the most important somatic effect of low doses of ionizing radiation. It is therefore of great concern to assess the quantitative cancer risk of exposure to radiations of different quality and to obtain information on the dose-response relationships for carcinogenesis. Tissues in the human with a high sensitivity for cancer induction include the bone marrow, the lung, the thyroid and the breast in women. If the revised dosimetry estimates for the Japanese survivors of the atomic bomb explosions are correct, there is no useful data base left to derive r.b.e. values for human carcinogenesis. As a consequence, it will be necessary to rely on results obtained in biological systems, including experimental animals, for these estimates. With respect to radiation protection, the following aspects of experimental studies on radiation carcinogenesis are of relevance: Assessment of the nature of dose-response relationships. Determination of the relative biological effectiveness of radiations of different quality. Effects of fractionation or protraction of the dose on tumour development. For the analysis of tumour data in animals, specific approaches have to be applied which correct for competing risks. These methods include actuarial estimates, non-parametric models and analytical models. The dose-response curves for radiation-induced cancers in different tissues vary in shape. This is exemplified by studies on myeloid leukaemia in mice and mammary neoplasms in different rat strains. The results on radiation carcinogenesis in animal models clearly indicate that the highest r.b.e. values are observed for neutrons with energies between 0.5 and 1 MeV. On the basis of such results it might be concluded that the maximum quality factor of 10 for neutrons should be increased. Based on current evidence, an increase by a factor of 2 to 3 seems more realistic than a tenfold rise. The diversity of dose-response relationships point to different mechanisms involved in the induction of different tumours in various species and even in different strains of the same species.
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PMID:Radiation carcinogenesis in experimental animals and its implications for radiation protection. 389 67

Lymphocytes from the spleen of BALB/Mo mice, which carry endogenous Moloney murine leukemia virus (M-MuLV), show in vitro frequencies of sister chromatid exchanges (SCEs) significantly higher than lymphocytes from control (M-MuLV free) BALB/c mice. In vitro treatment of lymphocytes with the antiviral antibiotic cordycepin (10 micrograms/ml) lowers the level of SCEs in BALB/Mo cells to the same value of BALB/c cells. M-MuLV yield is also markedly reduced in BALB/Mo lymphocytes cultured in the presence of cordycepin. The drug also abolishes the increased sensitivity of BALB/Mo lymphocytes to the induction of SCEs by mitomycin C (MMC) either in vitro (3 X 10(-8)/10(-7)M) or in vivo (0.3/3 mg/kg). Since cordycepin is known to inhibit poly(A)synthesis thus blocking RNA maturation, it is suggested that M-MuLV proviral integration is not per se the sole factor responsible for the more pronounced susceptibility of BALB/Mo lymphocytes to SCE induction, but most likely viral gene expression and amplification are needed for this effect to occur.
Carcinogenesis 1985 Jan
PMID:Cordycepin reduces the sensitivity of BALB/Mo mouse lymphocytes to the induction of sister chromatid exchanges. 391 67


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