Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [3H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase. Basal activities in both lymphoma lines were 3-4-fold greater than in mouse L1210 leukaemia cells. However, total endogenous poly (ADP-R) polymerase activity in both L5178Y cell lines, stimulated by a large excess of DNase in the presence of Triton X-100, was less than half the activity in L1210 cells. Doses of N-methyl-N-nitrosourea (MNU) that produced 20-50% survival of colony-forming units increased poly (ADP-R) in both lymphoma lines by only 25% compared with 377% in L1210 cells when synthesis was measured immediately after a 30-min exposure of MNU. During the first 24 h after MNU AII cells produced a peak of activity that was not seen with LS cells. A second peak was seen in both cell lines between 24 and 48 h following MNU. Concentrations of 3-aminobenzamide (3AB) above 2.5 mM inhibited colony-forming ability of lymphoma cells and equally inhibited uptake of [14C]formate into protein, RNA and DNA indicating that 3AB behaves as a general metabolic poison. Concentrations of 3AB in the toxic range of 3-10 mM inhibited poly (ADP-R) synthesis but no degradation of the polymer was observed. Non-toxic concentrations of 3AB potentiated cell killing by MNU to a similar degree in both lymphoma cell lines. In conclusion, we have found little evidence to support the hypothesis that the differential sensitivity of LS and AII is related to poly ADP-ribosylation. Compared with other mouse cells, L5178Y cells appear deficient in poly (ADP-R) polymerase and poly (ADP-R) glycohydrolase activities.
Carcinogenesis 1985 Jul
PMID:Poly (ADP-ribose) metabolism in alkylated mouse L5178Y cells. 299 Jul 53

We have examined the spleen DNA of individual mice of the RFM/Un strain for evidence of re-integration of the endogenous ecotropic provirus in radiation-induced and spontaneous neoplasms. The ecotropic env specific probe detects only a single 19 kb EcoRI or a single 7.0 kb HindIII fragment in all DNA preparations from normal tissues of RFM mice, corresponding to the endogenous provirus. Additional DNA restriction fragments containing the ecotropic virus (eco) specific sequence, corresponding to somatically acquired provirus, are detected in two out of five spleen DNA samples from animals with myeloid leukemia and one of three with thymic lymphoma. In addition somatically acquired eco-specific fragments are also detected in greater than 85% of DNA samples from reticulum cell sarcomas, a late occurring spontaneous hematopoietic neoplasm in this mouse strain. These results are consistent with a 'promoter/enhancer insertion' model of leukemogenesis involving the endogenous ecotropic provirus and are of particular interest since the RFM/Un mouse possesses a locus that restricts exogenous infection of cells by the endogenous virus.
Carcinogenesis 1986 Apr
PMID:Hematopoietic neoplasias of the RFM/Un mouse contain somatic re-integration of the restriction endogenous ecotropic provirus. 300 44

Previous results obtained in our laboratory suggested that natural antibodies reactive with L5178Y lymphoma cells play a role in the induction of lung tumors by the chemical carcinogen urethane. In order to characterize some of the naturally-occurring L5178Y reactive antibodies we prepared hybridomas that secreted natural monoclonal IgM antibodies reactive with L5178Y lymphoma cells. In the present study we characterized some of these antibodies and provided further proof as to their role in urethane carcinogenesis. One hybridoma secreted a cytotoxic antibody that reacted only with mouse lymphoma cell lines. Other non-cytotoxic monoclonal L5178Y-reactive antibodies showed various degrees of cross-reactivity with syngeneic, allogeneic and xenogeneic cells of normal or malignant origin. One of these antibodies reacted much better with activated T cells than with resting ones. Four groups of mice were treated with urethane. Three groups were injected twice a week during 5 months with different IgM preparations of natural monoclonal antibodies. The mice in the fourth group were not treated with IgM and served as controls. Five months after the urethane treatment the mice were sacrificed and the number of tumor foci in the lungs of each mouse was determined. The results show that the group treated with the cytotoxic monoclonal antibody 1.80 had a significant decrease, while the group treated with the IgM myeloma protein 104E had a significant increase in the number of tumor foci compared to urethane-treated mice that did not receive any IgM treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The immune system during the precancer period: naturally-occurring tumor reactive monoclonal antibodies and urethane carcinogenesis. 316 48

Growth of established murine tumor lines in media containing the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), was associated with reversible reductions in sensitivity to in vitro and in vivo parameters of natural resistance. L5178Y-F9 cells exposed to 100 ng TPA/ml for 2 days and returned to culture without TPA for 0-2 days, exhibited reductions in sensitivity to complement-mediated lysis by natural antibodies (Nab), activated macrophages and hypotonic lysis. The natural killer (NK) cell sensitive SL2-5 lymphoma was less sensitive to NK cells, complement-dependent NAb and hypotonic lysis after 2 days growth in 2 or 3 micrograms TPA/ml. Although TPA-treated L5178Y-F9 cells could acquire higher levels of serum NAb in vitro, this was complicated by the instability of the binding at 37 degrees C resulting in an effectively reduced capacity to bind NAb which was also demonstrated by TPA-treated SL2-5 cells. The tumor frequency of threshold s.c. inocula and the i.v. metastatic potential of the TPA-treated tumors was increased in syngeneic DBA/2 mice revealing possible correlations between reductions in the cellular characteristics assayed in vitro and decreased susceptibility to host-mediated defenses in vivo. Continued growth of the TPA-treated cells for a total of 2-8 days without TPA produced a reversal in the in vitro parameters, in the tumor frequency and in the metastatic potential, indicating the requirement for TPA to maintain the resistant phenotype. These data are consistent with the initial reversible nature of the promotion phase of multistage carcinogenesis. The reversible TPA-induced reductions in sensitivity to mediators of natural resistance may be an integral component of promotion, contributing to tumor survival in vivo and increasing the probability that the tumor will progress to a more malignant phenotype.
Carcinogenesis 1988 Nov
PMID:Tumor progression in vitro: tumor-promoter-induced reversible decrease in natural immune susceptibility. 318 Mar 34

We have previously demonstrated that cyclosporine (CsA), a powerful immunosuppressant, enhanced the development of thymic lymphomas in Swiss Webster mice initiated with a single subcarcinogenic dose of N-methyl-N-nitrosourea and enhanced the spontaneous development of thymic tumors in AKR mice. In the present study, we examined whether the initiation of mice with a single dose of gamma-radiation modified the target cell specificity of the CsA promotion of lymphoma induction. Male Swiss Webster and C57B/6 mice were divided into four groups. The mice in group 1 and 2 of both strains were given a single dose (350 rad) of gamma-radiation; 10 days thereafter group 1 was given a basal diet and group 2 a basal diet containing 0.015% CsA for 25-35 weeks. Groups 3 and 4 consisted of control mice without radiation and were maintained on a basal or a CsA diet. None of the mice in either strain in groups 1, 3 and 4 developed tumors. Eighteen out of 39 (46%) Swiss Webster mice that received radiation followed by a CsA diet developed tumors involving mesenteric lymph nodes and the spleen. The tumor cells had immunoglobulins on their surface and were negative for Thy 1, suggesting lymphomas of B cell lineage. Four mice (10%) developed thymic tumors which were positive for Thy 1. Seven of 14 (50%) C57B/6 treated with radiation and CsA developed thymic tumors, while none developed tumors of B cell lineage. The results indicate that CsA is a potent promoter of the induction of lymphomas in mice and that the cell type is determined by the type of initiating agents and the strain of mice.
Carcinogenesis 1988 Jun
PMID:Diversity of the promoting action of cyclosporine on the induction of murine lymphoid tumors. 328 29

The tissue distribution of radioactivity 1 h after i.p. injection of [n-propyl-2,3-3H]1-n-propyl-1-nitrosourea (PNU) (100 mg/kg) was studied in male F344 rats. This treatment results in a high incidence of thymic lymphomas. The 3H concentration in the thymus, testis and brain was significantly higher than that in blood. 7-n-propylguanine and O6-n-propylguanine were detected in thymus DNA of F344 rats treated with PNU; the ratio of O6-n-propylguanine/7-n-propylguanine was 0.35, lower than following DNA alkylation in vitro. This suggests the presence of O6-alkylguanine DNA alkyltransferase (AGT) in thymus. AGT activity in F344 and Long-Evans rats was compared by using a 3H-propylated DNA as a substrate. AGT activity in the thymus of F344 rats was lower than that in the liver. The AGT activity in the thymus of Long-Evans strain, which had a low incidence of PNU-induced thymic lymphomas, was higher than that of F344 strain. The high level of DNA alkylation by PNU and the low activity of AGT in the thymus may contribute to the high incidence of thymic lymphoma in F344 rat.
Carcinogenesis 1988 May
PMID:Alkylation of DNA in F344 rat thymus following administration of 1-n-propyl-1-nitrosourea in vivo and comparison of O6-alkylguanine DNA alkyltransferase activity in thymus from F344 and Long-Evans rats in vitro. 336 46

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.
 ...
PMID:Oil gavage effects on tumor incidence in the National Toxicology Program's 2-year carcinogenesis bioassay. 359 39

People living in the industrial society of today are unavoidably exposed to low-energy electromagnetic (EM) radiation. The potential risk to human health of such exposure has received much study. In this regard, numerous epidemiological studies have linked exposure to low-energy EM fields to increased cancer risk. We investigated the ability of low-energy 60-Hz EM fields to alter the activity of ornithine decarboxylase (ODC) in a number of established cell lines. The activity of ODC, the controlling enzyme in polyamine biosynthesis, has been shown to be elevated in growing cells or tissues and during the process of tumor promotion. A 1-h exposure to a 60-Hz EM field of an intensity of 10 mV/cm produced a 5-fold increase in ODC activity in human lymphoma CEM cells and a 2- to 3-fold increase in mouse myeloma cells (P3) relative to the unexposed cultures. Depending upon the cell type, ODC activity increased during the 1-h exposure period and remained elevated for several hours after the field exposure ended. In another series of experiments, fields of an intensity as low as 0.1 mV/cm for a 1-h period produced a 30% increase in the activity of ODC in Reuber H35 hepatoma cells grown in monolayer culture. In the H35 cells, continuous exposure to the 60-Hz EM field (10 mV/cm) for periods of 2 and 3 h resulted in either no increase in ODC activity (2 h) or a decrease in enzyme activity (3 h) compared to the unexposed control cultures. The data is discussed in relation to possible molecular mechanisms of field-cell interaction, the importance of the exposure intervals altering cellular ODC activity and the potential ability of 60-Hz EM fields to serve as a tumor promoting stimulus.
Carcinogenesis 1987 Oct
PMID:The effects of low-energy 60-Hz environmental electromagnetic fields upon the growth-related enzyme ornithine decarboxylase. 365 76

Chronic exposure to 1,3-butadiene (BD) results in a marked increase in the incidence of thymic lymphoma in male B6C3F1 relative to NIH Swiss mice whereas no demonstrable differences in bone marrow (target organ) toxicity exist. Repeated exposure to BD is known to produce a macrocytic anemia and an increase in the frequency of micronuclei in circulating erythrocytes in both strains. The present study was undertaken to determine if chromosomal breakage, aneuploidy or both reflect differences in BD leukemogenicity observed between B6C3F1 and NIH Swiss mice. Mice were exposed to a single concentration of BD (1250 p.p.m.) for 6 h. Bone marrow cell preparations were made at 24, 48, 72 and 96 h after cessation of exposure. In both strains comparable increases in the frequency of chromosomal aberrations (of the chromatid type) were observed following exposure to BD. Significant differences in the number of chromosomes were not observed, although a pattern of chromosomal loss in cells from treated animals was observed. These results indicate that BD-treatment in vivo produces significant increases in chromatid aberrations but not aneuploidy in both strains. Therefore it is concluded that bone marrow toxicity, including cytogenetic abnormalities, is not predictive of leukemogenicity in these mice.
Carcinogenesis 1987 Nov
PMID:Chromosome aberrations in mouse bone marrow cells following in vivo exposure to 1,3-butadiene. 366 63

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), which is a potent mutagen from pyrolysates of tryptophan, was given subcutaneously to neonatal ICR mice, and all animals were observed for 1 year. Tumors of the livers and lymphoreticular tissue were induced. In the mice given Trp-P-1, the incidences of these tumors were as follows: liver tumors in 45% of the males; malignant lymphoma in 13% of the males and in 24% of the females. In the mice given Trp-P-2, the incidences of liver tumors in the males were dose-dependent (12.5 mg/kg, 12%; 25 mg/kg, 18%), while those of malignant lymphoma varied within a range from 5 to 19%. Statistical analysis revealed that the incidences of the liver tumor in the mice given Trp-P-1 or Trp-P-2 and those of lymphoma in the mice given Trp-P-1 were significantly higher than those of the controls. In the control mice, the incidences of tumors were as follows: malignant lymphoma in 5% of the females; lung tumor in 14% of both sexes.
Carcinogenesis 1987 Nov
PMID:Tumor induction in mice administered neonatally with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole or 3-amino-1-methyl-5H-pyrido[4,3-b]indole. 366 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>