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

Four inbred strains of mice (C3H/HeJ, C57BL/6J, AKR/J, and DBA/2J) were injected s.c. with 150 micrograms of dibenz[a,h]anthracene and followed for 9 months. Strains C3H/HeJ and C57BL/6J were most susceptible to dibenz[a,h]anthracene-induced carcinogenesis with 80% and 53% incidence of tumors, respectively. Strains AKR/J and DBA/2J were much less sensitive with only one tumor observed out of a total of 60 treated mice. Dibenz[a,h]anthracene was shown to induce hepatic aryl hydrocarbon hydroxylase activity in the two sensitive strains, C3H/HeJ and C57BL/6J, but not in the two resistant strains, AKR/J and DBA/2J. When 3-methylcholanthrene-treated liver microsomes from the four strains were studied for dibenz[a,h]anthracene metabolism in vitro, the two sensitive strains not only demonstrated a 3- to 4-fold greater overall rate of metabolism than the two resistant strains, but also showed a quantitative shift with a greater percentage of the total metabolites being the 3,4-diol of dibenz[a,h]anthracene. This diol is the presumed precursor to the apparent ultimate carcinogen, dibenz[a,h]anthracene 3,4-diol-1,2-epoxide.
Carcinogenesis 1983
PMID:Dibenz[a,h]anthracene-induced subcutaneous tumors in mice. Strain sensitivity and the role of carcinogen metabolism. 685 Sep 80

Feeding of choline-devoid (CD) diet and dietary administration of phenobarbital (PHB) are efficient promoters of liver carcinogenesis in the rat. Furthermore, inclusion of PHB in a CD diet results in a synergistic effect, inasmuch as the promoting action of their combination is greater than the sum of those exerted by either agent alone. To investigate the mechanism(s) of action of the two promoters, liver DNA synthesis and liver cell proliferation were studied in rats fed a CD diet, a choline-supplemented diet, or the same diets to which 0.06% PHB was added. DNA synthesis was determined by [3H]thymidine incorporation into DNA and autoradiography, and cell proliferation was determined by mitosis counts. Feeding the CD diet caused an increase of both DBA synthesis and cell proliferation over those present in rats fed the choline-supplemented diet. Inclusion of PHB in the CD diet, on the other hand, inhibited DNA synthesis and cell proliferation. These results indicate that stimulation of cell proliferation per se may not be a sufficient condition for an agent to act as a promoter of liver carcinogenesis.
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PMID:Stimulation of DNA synthesis and cell proliferation in the liver of rats fed a choline-devoid diet and their suppression by phenobarbital. 705 94

C3H, CBA, C57BL/6j, (CBA x C57BL/6j)F1, BALB/c, DBA/2, C3HA and AKR female mice were treated with 25 weekly s.c. injections of a solution of 1,2-dimethylhydrazine (DMH) in water at a dose level of 8 mg/kg body weight. BALB/c mice appeared to be most sensitive to the induction of epithelial colorectal (93.3%) and anal tumours by DMH. There was, however, a dissociation between the severity of the macroscopical tumour lesions in the colon of BALB/c mice and their relatively weak tendency to infiltrative growth. C3HA mice were more resistant to the induction of intestinal tumours (30.9%) but the tumours showed a deep invasion into the intestinal wall. There was no correlation between the strains and within a given strain between the development of colorectal and anal neoplasms. C3H and CBA mice strains developed a high incidence of uterine sarcomas (37.5 and 40.7%, respectively) which were not found at all in BALB/c, DBA/2 and C3HA mice and which appeared in C57BL/6j and AKR mice at low frequency (2.7 and 7.7%, respectively). C57BL/6j, BALB/c, DBA/2 and C3HA mice developed haemorrhagic lesions of the ovaries (35.1, 46.7, 62.9 and 85.7%, respectively). These lesions, which led to peritoneal haemorrhage, were one of the main causes of death in C3HA and DBA/2 strains. It seems that, with the exception of AKR mice, an inverse relationship exists between the occurrence of haemorrhagic ovarian lesions and development of uterine sarcomas in female mice treated with DMH.
Carcinogenesis 1982
PMID:Strain differences in susceptibility of female mice to 1,2-dimethylhydrazine. 711 53

A series of experiments was conducted to determine the efficacy of 15 synthetic retinoic acid amides (retinamides) as inhibitors of chemical carcinogenesis of the urinary bladder in C57BL/6 x DBA/2F1 mice. Eight of the retinamides tested had significant protective activity when administered at nontoxic levels in the diet. Minor structural alterations, such as the addition of a methyl or hydroxyl group to the terminal amide moiety had a major influence on the anticarcinogenic activity of the retinamides. Although 13-cis retinamides generally were less toxic on a molar basis than were their all-trans isomers, no consistent pattern of differential anticarcinogenic activity was noted among the six pairs of all-trans and 13-cis isomers tested. All-trans-4-hydroxyphenyl retinamide was among the most active and least toxic of the retinoids tested, and appears to be the compound of choice for further study.
Carcinogenesis 1982
PMID:Influence of 15 retinoic acid amides on urinary bladder carcinogenesis in the mouse. 715 Dec 60

The ability of cytosolic 3-methylcholanthrene binding proteins from rat liver to interact with DNA was studied using DNA-cellulose chromatography. Two DNA binding fractions, eluting in 0.15 M KCl (peak 1) and 0.33 M KCl (peak 2), were observed on salt elution from a denatured DNA-cellulose column which had been incubated with rat liver cytosol containing radiolabelled 3-methylcholanthrene. No detectable DNA binding fractions were found when columns containing cellulose alone or native DNA-cellulose were used. Temperature activation of the cytosolic proteins containing 3-methylcholanthrene did not result in a significant difference in DNA binding characteristics when compared with a non-treated sample. The pretreatment of rats with Aroclor 1254 induced peak 1 3.7 fold over control values. An analysis of the proteins present in peaks 1 and 2 from control and induced rats was carried out using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Comparative DNA-cellulose chromatography of cytosolic liver proteins from a cytochrome P-448 inducible mouse strain (DBA/6J) and non-inducible mouse strain (DBA/2J) showed much higher levels of DNA binding by protein bound 3-methylcholanthrene from C57BL/6J hepatic cytosol.
Carcinogenesis 1980 Jun
PMID:Interaction of DNA with cytosolic 3-methylcholanthrene binding proteins from either rat or mouse liver. 727 80

The susceptibility of sister chromatid exchange (SCE)-induction in bone marrow cells by cyclophosphamide (CPA) was tested in DBA/2, AKR, C57BL/6J, C3Hf and BALB/c mice in vivo. Mice were treated with one i.p. injection of 0.4, 2.0 and 10.0 mg/kg body weight of CPA or of saline. The base-line level of SCE was similar in all the strains with about 3 SCE/cell. Increasing concentrations of CPA caused an increased level of SCE. At any dose level, differences in the SCE frequency were observed among the five strains. The greatest difference was seen at the dose of 10 mg/kg, when the DBA/2 strain reached the frequency of 25.5 SCE/cell, whereas 19.3, 12.9, 11.4 and 10.1 SCE/cell were seen respectively in AKR, C57BL/6J, C3Hf and BALB/c mice.
Carcinogenesis 1981
PMID:Differences in sister chromatid exchange (SCE)-induction in vivo by cyclophosphamide in murine strains. 727 6

Dose-response relationships in the induction of urinary bladder cancer in male C57BL/6 x DBA/2-F1 (BDF) mice by intragastric instillation of N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) were studied. Administration of a total dose of 0 to 80 mg OH-BBN in 10 weekly fractions to groups of 25 mice resulted in a linear increase in carcinoma incidence with dose. OH-BBN administration schedule had a significant effect on cancer incidence: administration of a total dose of 30, 20, or 15 mg OH-BBN in 20 weekly fractions was more effective in cancer induction than was the same total dose given in 5 fractions. A 10 dose administration schedule was of intermediate efficacy. The data obtained indicate that OH-BBN induces urinary bladder cancers in BDF mice in a dose-related manner, with high target organ-specificity, little toxicity, and short tumor latency; induced tumors are primarily transitional cell carcinomas which morphologically resemble their human counterpart. Administration of OH-BBN mice provides a useful model for the experimental study of urinary bladder cancer.
Carcinogenesis 1981
PMID:Influence of total dose and dose schedule on induction of urinary bladder cancer in the mouse by N-butyl-N-(4-hydroxybutyl)nitrosamine. 727 10

Altered expression of ABH blood group substances is a common feature of human colorectal carcinoma, yet it remains unclear how these structural changes influence the biological properties of tumor cells. Azoxymethane-induced rat colon tumors display many features of the human disease, thereby providing a potentially useful model to study the role of blood group substances in colon cancer progression. We have prepared monoclonal antibodies to a microsomal fraction isolated from an azoxymethane-induced rat colon tumor and selected an antibody that detects cancer-associated changes. Monoclonal antibody (mAb) 3A7 recognizes a determinant on type 2 chain blood group A (GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) and B (Gal alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) oligosaccharides. Expression of the epitope detected by this antibody was developmentally regulated in rat colon, with maximal expression from day 4-21 after birth. Immunohistochemical staining and Western blotting analyses of azoxymethane-induced colon tumors revealed increased expression of the epitope in all of the 21 colonic tumors examined, including preneoplastic glands within transitional mucosa. Conventional and signet-ring adenocarcinomas that had invaded through the muscularis propria (Duke's B2) consistently showed the most intense staining with mAb 3A7, including regions depicting angioinvasion. Some of the lymph node metastases (Duke's C2) stained poorly with the antibody. The epitope was also expressed in blood group A positive human colon carcinoma cell lines, including HT29 and SW480 but not by SW620, a cell line derived from a lymph node metastasis isolated in vivo from the SW480 primary tumor, or in the blood group B cell line SW1417. The glycoproteins detected by mAb 3A7 in rat colon tumors and HT29 cells ranged in size between 50 and 200 kd, including a major species of 140 kd. Affinity chromatography of detergent lysates of normal rat colon on the blood group A specific lectin Dolichos biflorus (DBA)-agarose resulted in nearly quantitative binding of glycoprotein species detected by the antibody. By contrast, immunoreactive glycoproteins from rat colon tumors or HT29 cells bound poorly to DBA-agarose but were retained by another blood group A-binding lectin, Helix-pomatia (HPA)-agarose. These results indicate that colon carcinogenesis results in quantitative as well as qualitative changes in oligosaccharides detected by mAb 3A7 and suggest that the combined use of mAb 3A7 and blood group A-specific lectins may provide a useful tool for early detection of colon cancer.
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PMID:Monoclonal antibody recognizing a determinant on type 2 chain blood group A and B oligosaccharides detects oncodevelopmental changes in azoxymethane-induced rat colon tumors and human colon cancer cell lines. 753 50

Repetitive treatment with the organotropic colon carcinogen, 1,2-dimethylhydrazine (DMH), produces tumors in susceptible mouse strains that exhibit pathological features associated with the human disease. As in human populations, the genetic background of laboratory animals comprises a significant component to this organ-specific carcinogenesis, and several mouse lines, including AKR/J and DBA/2J are highly resistant to the tumorigenic effects of DMH. During the course of ongoing studies to establish phenotypic differences between susceptible (SWR/J and P/J) and resistant strains, we have examined the colonic mucosa of DMH-treated mice for the presence of aberrant crypt foci (ACF). ACF represent an early morphological lesion in stepwise progression of colon cancer. In Experiment 1, 6-week-old SWR/J and AKR/J mice were injected with DMH (35 and 20 mg/kg, respectively) once a week for 2 weeks. Five weeks later, colons were removed and ACF visualized at low magnification by light microscopy after methylene blue-staining. Only SWR/J mice revealed focal atypia indicative of preneoplastic change. To obtain additional information about their morphology, tissue sections containing ACF were sectioned and stained with H&E. ACF are larger and have a thicker epithelial lining than normal crypts. H&E confirmed the absence of these lesions in untreated SWR/J and DMH-exposed AKR/J mice. In Experiment 2, SWR/J and DBA/2J mice were injected with DMH (35 mg/kg) once a week for 2 weeks. Nine weeks later, colons were analyzed for ACF formation. Comparable to the first experiment, no ACF were observed in the colonic mucosa of the resistant DBA/2J line. In contrast, ACF were readily identified in the middle and distal colons of similarly exposed SWR/J mice. This differential response between resistant and susceptible mouse lines further supports an important role for ACF in the stepwise progression of colon cancer.
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PMID:Induction of aberrant crypts in murine colon with varying sensitivity to colon carcinogenesis. 760 May 32

Both male DBA/2J and C3H/HeJ mice are highly susceptible to hepatocarcinogenesis induced by experimental treatment with N,N-diethylnitrosamine (DEN) relative to male C57BL/6J mice. While C3H/HeJ mice carry multiple sensitivity loci, designated Hcs (hepatocarcinogen sensitivity), our previous study indicated that the susceptibility of DBA/2J mice results from the combined effects of multiple sensitivity loci and two major resistance loci, Hcr-1 and -2 (hepatocarcinogen resistance). We proposed that BXD-15 recombinant inbred mice, which are extremely resistant to DEN-induced hepatocarcinogenesis, may carry the Hcr loci from the parental DBA/2J mice, but few, if any, of the multiple sensitivity loci. Conversely, the extremely sensitive BXD-11 recombinant inbred mice may carry most of the multiple sensitivity loci of the DBA/2J parents, but neither of the major resistance loci. In order to confirm our genetic model for hepatocarcinogenesis in DBA/2J mice and to evaluate the phenotypic effects of the Hcr loci on the Hcs loci of C3H/HeJ mice, we characterized hepatocarcinogen sensitivities of F1 mice generated from the crosses involving BXD-11, BXD-15, C3H/HeJ and C57BL/6J strains. When male mice were initiated with DEN at 12 days of age and liver tumors were enumerated at 32 weeks of age, (BXD-15 x BXD-11)F1 mice had one sixth the number of liver tumors observed in (C57BL/6J x BXD-11)F1 mice, consistent with our previous conclusion that DBA/2J mice possess hepatocarcinogen resistance genes in spite of their high susceptibility to DEN. Significantly, (C57BL/6J x C3H/HeJ)F1 mice also had a 2.3-fold greater number of liver tumors and 5.5-fold higher total volume of initiated lesions per liver as compared with (BXD-15 x C3H/HeJ)F1 mice, indicating that the hepatocarcinogen resistance genes inherited by BXD-15 mice are capable of suppressing the Hcs phenotype. Thus the Hcr loci may influence a wide variety of hepatocarcinogen sensitivity loci and be able to act as general resistance loci for chemical hepatocarcinogenesis. Stereological analysis of initiated hepatocellular lesions with glucose 6-phosphatase deficiency revealed that the resistance genes largely influence the promotion stage of hepatocarcinogenesis.
Carcinogenesis 1995 Aug
PMID:The Hcr (hepatocarcinogen resistance) loci of DBA/2J mice partially suppress phenotypic expression of the Hcs (hepatocarcinogen sensitivity) loci of C3H/HeJ mice. 763 31


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