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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of experimental tobacco smoke carcinogenesis have suffered from the lack of a conveniently available and well-characterized device for exposing animals to tobacco smoke for inhalation. The Walton Horizontal Smoking Machine, a commercially available system designed to expose up to 20 mice to the smoke of a single cigarette, may fulfill this need. This system produced a uniform smoke aerosol of predictable concentration and appropriate composition for cigarettes with high delivery of nicotine (40 mg total particulate matter, 2.6 mg nicotine, and 17 cm3 carbon monoxide per cigarette) and with low delivery of nicotine (30 mg total particulate matter, 0.3 mg nicotine, and 17 cm3 carbon monoxide). In this experiment C57BL and DBA/2Bd strains of mice were used. Limitations of the concept of exposing animals to standing smoke were defined.
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PMID:Inhalation bioassay chemistry--Walton Horizontal Smoking Machine for inhalation exposure of rodents to cigarette smoke. 28 32

Pyrolysis products of proteins and amino acids are highly mutagenic, but metabolism of these chemicals by rat liver subcellular fractions is known to be required for production of the mutagenic intermediates. We examined the mutagenesis of seven purified pyrolysis products from tryptophan, lysine, glutamic acid, and soybean globulin with Salmonella typhimurium strain TA98 in the presence of liver fractions from genetically "responsive" C57BL/6N and Ah(b)/Ah(d) or "nonresponsive" DBA/2N and Ah(d)/Ah(d) mice that had been pretreated in vivo with benzo[a]pyrene. For all pyrolysis products tested, mutagenesis is 2-fold to more than 1000-fold greater with C57BL/6N and Ah(b)/Ah(d) than with DBA/2N or Ah(d)/Ah(d) liver fractions. A sucrose density gradient assay for detecting the Ah regulatory gene product, the receptor, was studied with C57BL/6N hepatic cytosol. At levels 100 times in excess of [1,6-(3)H]2,3,7,8-tetrachlorodibenzo-p-dioxin, nonlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and beta-naphthoflavone (inducers of cytochrome P(1)-450) are able to displace the radioligand from its hepatic cytosolic receptor; four pyrolysates from tryptophan, glutamic acid, and soybean globulin did not have this capacity. These data indicate that the pyrolysis products tested, although not effective as inducers of cytochrome P(1)-450, are most mutagenic when metabolized by P(1)-450. Potent P(1)-450 inducers-present in pyrolysates during the combustion process-might be present in quantities insufficient to initiate mutagenesis or carcinogenesis but might have a synergistic action, or act as "comutagens" or "cocarcinogens," with the N-containing heterocyclic pyrolysis products. A quantitative relationship between mutagenic and carcinogenic potency of these pyrolysis products remains, however, to be demonstrated.
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PMID:Pyrolysis products from amino acids and protein: highest mutagenicity requires cytochrome P1-450. 29 93

Effect of 1,1,1-trichloropropene 2,3-oxide and 7,8-benzoflavone on benzo[a]-pyrene and 3-methylcholanthrene carcinogenesis in the subcutaneous tissues of C3H/He and DBA/2 mice was examined. By a single application of the carcinogen, the incidence of fibrosarcoma was higher and the latency of tumorigenesis was shorter in C3H/He mice than in DBA/2 mice. Treatment with 1,1,1-trichloropropene 2,3-oxide increased the incidence of fibrosarcoma in DBA/2 mice, but decreased the rate in C3H/He mice, when benzo[a]pyrene was used as a carcinogen. On the other hand, in 3-methylcholanthrene carcinogenesis, no effect of the oxide on the tumor incidence was observed. By the simultaneous application of 7,8-benzoflavone with benzo[a]pyrene, the tumor incidence increased, but not so significantly in DBA/2 mice, compared to that treated with benzo[a]pyrene alone, and no appreciable effect was observed in C3H/He mice treated with benzo[a]pyrene, and in both strains of mice with 3-methylcholanthrene. The relationship between the activity of arylhydrocarbon hydroxylase and the change in polycyclic hydrocarbon carcinogenesis is briefly discussed.
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PMID:Effect of trichloropropene oxide and benzoflavone on polycyclic hydrocarbon carcinogenesis in C3H/He and DBA/2 mice. 44 77

The immunosuppressive effects of 3-methylcholanthrene (MCA) given intratracheally have been shown to correlate with susceptibility of some inbred strains of mice to MCA-induced carcinogenesis. In susceptible strains of mice, C3Hf and C57BL/6, intratracheal administration of MCA resulted in profound systemic immunodepression. This effect was not observed in resistant DBA/2 mice. This immunodepressive effect correlated with the inducibility of the aryl hydrocarbon hydroxylase enzyme complex and the inducibility of pulmonary tumors by MCA.
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PMID:Immunosuppressive effects of 3-methylcholanthrene given intratracheally in various inbred strains of mice. 90 29

Several studies have indicated a correlation between the presence of inflammation and the development of cancer. The aim of our study was to determine if pulmonary neutrophils could transform the proximate respiratory carcinogen (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-diol), to an ultimate carcinogenic metabolite via myeloperoxidase (MPO). To test this hypothesis, virus-free male DBA/2 mice were exposed by inhalation to the Gram-negative bacteria Proteus mirabilis for 1 h. For various time points post-exposure, bronchoalveolar lavage (BAL) was performed to determine total and differential cell counts, cellular MPO activity and production of superoxide. Twelve hours after the exposure, cellular activity of MPO as well as percentage and total number of polymorphonuclear leukocytes peaked and declined thereafter. At this same time point, cells from BAL exhibited increased release of superoxide, as measured by reduction of cytochrome c, after addition of soluble or particulate stimuli, 12-O-tetradecanoylphorbol-13-acetate (TPA) or opsonized zymosan respectively. These cells also elicited biotransformation of B[a]P-7,8-diol as evidenced by enhanced B[a]P-7,8-diol-derived chemiluminescence, tetraol formation and covalently bound adduct formation to exogenous DNA upon addition of TPA or opsonized zymosan. Moreover, the cell-free BAL fluid of infected mice contained substantial MPO activity in comparison to that of uninfected animals. Also, MPO enhanced the binding of B[a]P-7,8-diol to lung DNA in vitro. Unlike previous work emphasizing the potential roles of oxygen free radicals in tumor promotion, our results indicate a role of neutrophilic MPO in the initiation of carcinogenesis.
Carcinogenesis 1992 Jul
PMID:Myeloperoxidase-enhanced formation of (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene-DNA adducts in lung tissue in vitro: a role of pulmonary inflammation in the bioactivation of a procarcinogen. 132 50

The tumor-promoting and carcinogenic effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in the liver and in other organs were quantified and compared to those of phenobarbital (PB) in two inbred strains of mice (C57BL/6NCr, DBA/2NCr) and in F344/NCr rats initiated at 5 weeks of age with N-nitrosodiethylamine (NDEA; 90 mg/kg in mice, 75 mg/kg in rats). Two weeks later animals were placed on a regimen of TCPOBOP once every 2 weeks (administered i.p. or i.g.) or on a diet containing 500 p.p.m. PB as a positive control for the duration of the experiment. Mice were administered TCPOBOP (3.0 mg/kg/dose) for 30 weeks followed by control diet, while rats were given the TCPOBOP regimen (3.0 or 30 mg/kg/dose) for the full 78 weeks of the experiment. TCPOBOP was a complete carcinogen and an extremely potent promoter in both strains of mice, particularly the DBA strain in which NDEA followed by TCPOBOP (i.p.) resulted in death of all the animals within 30 weeks from multiple hepatocellular tumors. TCPOBOP alone induced 100% tumor incidence in DBA mice within 60 weeks. In addition, in both strains of mice, a high proportion of those animals with liver tumors had metastases to the lungs. In contrast, TCPOBOP was ineffective as a liver tumor promoter in F344 rats at even 10 times the dose administered to mice. Interestingly however, TCPOBOP, when given subsequent to NDEA, caused a significant increase in nasal cavity tumors in F344 rats. PB was an effective liver tumor promoter in male DBA mice and male F344 rats, but was relatively ineffective as a promoter in C57 mice. When tumor-promoting activity and induction of cytochrome P450 IIB1 were compared, good agreement between these two parameters was observed. PB was an effective inducer of P450 IIB1 in the rats and in both strains of mice and a potent liver tumor promoter in both DBA mice and F344 rats, whereas TCPOBOP was a potent inducer and tumor promoter in both strains of mice but was negligibly effective as either an inducer or a promoter in F344 rats at even 10-fold higher dosage.
Carcinogenesis 1992 Oct
PMID:Tumor-promoting and hepatocarcinogenic effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in DBA/2NCr and C57BL/6NCr mice and an apparent promoting effect on nasal cavity tumors but not on hepatocellular tumors in F344/NCr rats initiated with N-nitrosodiethylamine. 133 Mar 46

Activation of the ras family of oncogenes occurs frequently in liver tumors of the B6C3F1 mouse, a strain which is highly sensitive to hepatocarcinogenesis. Many other mouse strains are much more resistant to hepatocarcinogenesis; the aim of this study was to determine the frequency and pattern of oncogene activation in spontaneous and chemically induced liver tumors of three such strains, the C57BL/6J, the C57BL/6 x DBA/2 F1 hybrid (B6D2F1) and the C57BL/6 x Balb/c F1 hybrid (B6BCF1). The C57BL/6, DBA/2 and Balb/c strains are all relatively resistant to spontaneous hepatocarcinogenesis (1.5-3.6% of animals develop liver tumors in 2 years); with regard to chemically induced hepatocarcinogenesis the Balb/c is highly resistant, the C57BL/6 has low susceptibility and the DBA/2 has low to moderate susceptibility. The nude mouse tumorigenicity assay was used to search for activated oncogenes in 15 C57BL/6J liver tumors induced by a single neonatal dose of vinyl carbamate (VC, 0.15 mumol/g body weight). Three tumors contained H-ras genes activated by point mutations at codon 61 and one contained a non-ras oncogene. The polymerase chain reaction and allele-specific oligonucleotide hybridization were used to study H-ras mutations in spontaneous and VC-induced tumors from all three strains of mice. The frequency of H-ras codon 61 mutations in tumors induced by 0.15 mumol/g body weight VC in the C57BL/6J mouse (5/37) was similar to that in spontaneous tumors (2/9); surprisingly, tumors induced by a lower dose of VC (0.03 mumol/g body weight) had a higher frequency of H-ras mutations (12/28). The frequencies of H-ras activation detected in VC (0.03 mumol/g body weight)-induced tumors from the two F1 hybrids studied differed markedly. Only one VC-induced B6BCF1 tumor contained a mutated H-ras gene (1/10), whereas the majority of B6D2F1 tumors contained such mutations (23/33). Several spontaneous B6D2F1 liver tumors contained H-ras codon 61 mutations (6/15). Thus, H-ras activation frequency does not determine susceptibility to hepatocarcinogenesis in inbred mice and their F1 hybrids, since a relatively high frequency of H-ras mutations was observed in two resistant strains and a low frequency was found in the other strain.
Carcinogenesis 1992 Dec
PMID:Proto-oncogene activation in liver tumors of hepatocarcinogenesis-resistant strains of mice. 136 83

Although the hamster pancreas does not express A, B or H blood group antigens, all hamster pancreatic ductal adenocarcinomas induced by treatment with N-nitrosobis(2-oxopropyl)amine express blood group-A antigen. Thus, the acquisition of blood group-A antigen expression in this system is a cancer-associated alteration. We have purified three major blood group-A antigen bearing glycoproteins (gp120, gp135 and gp150) from hamster pancreatic cancer cell membrane preparations using affinity chromatography on DBA (Dolichos biflorus) agglutinin-agarose. When assayed by immunoblotting, gp120 and gp135 showed strong blood group-A reactivity, which was removed by treating membrane samples with peptide-N-glycosidase F. Blood group-A reactivity was unchanged by treatment of the membrane fractions with endoglycosidases F and H. In addition, these two glycoproteins bearing blood group-A antigen also bound L-PHA (Phaseolus vulgaris leucoagglutinin). These results demonstrate that gp120 and gp135 express blood group-A antigen on Asn-linked multi-antennary complex type glycan structures. The gp150 showed weak blood group-A expression. This is the first demonstration of the neoexpression of cancer-associated blood group-A determinants which reside on Asn-linked glycan structures.
Carcinogenesis 1992 Oct
PMID:Purification and analysis of glycoproteins bearing blood group-A determinants from hamster pancreatic ductal adenocarcinomas. 138 1

Three model systems of plasmacytomagenesis that are associated with mutations that affect c-myc transcription were discussed. Plasmacytoma induction by chronic peritoneal irritation induced by non-metabolized paraffin oils or plastic objects is strongly influenced by the immune status of the host. BALB/cAn mice must be exposed to natural environmental antigens to develop a high incidence of plasmacytomas. This may be related to T-cell priming. BALB/cAn mice raised under strict SPF conditions are refractory to plasmacytoma induction by pristane. The genotype of the mouse plays an important role in the chronic peritoneal irritation model of plasmacytomagenesis in mice. Only a few of the standard inbred strains are susceptible, notably BALB/cAn and NZB/B1. The genetic basis of susceptibility and resistance has been studied in crosses and congenic strains involving the susceptible BALB/cAn and resistant DBA/2 strains. While several genes play a role in determining resistance at least one resistance gene located on the distal end of Chr 4 reduces the incidence by at least 50% as determined in the BALB/cAn.DBA/2 Fv-1n/n congenic strain. The action of susceptibility and resistance genes is not known; hypothetically these genes could play a role in plasmacytomagenesis by increasing the probabilities of illegitimate exchanges between genes or by influencing the formation of mutations in genes that regulate mitotic cycling. Plasmacytomas appear to develop in the chronic inflammatory tissues induced by these agents. Fundamental unanswered questions are whether these inflammatory tissues provide products such as oxidants in vivo that damage DNA and promote mutagenesis. In the mouse there is a resident self-renewing B cell population that is CD5+. These B cells, which are known to be precursors of normal lamina propria IgA-secreting plasma cells, are directly in contact with the chronic inflammatory process induced by pristane; they may be targets in plasmacytomagenesis. The plasmacytomas that develop by the peritoneal mode of induction all have chromosomal translocations that directly or indirectly activate c-myc. The predominant MACTR found in 90% of these tumors is T(12;15) in which a heavy-chain switch region sequence is joined to the 5' region of c-myc. The evidence strongly suggests that the translocation develops in a late mature B cell that is in the process of isotype switching. An unanswered question is whether the switching associated T(12;15) takes place in a B cell that is exposed to the inflammatory microenvironment.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1992 Oct
PMID:Plasmacytomagenesis in mice: model of neoplastic development dependent upon chromosomal translocations. 142 27

Chronic administration of tamoxifen to female rats causes hepatocellular carcinomas. We have investigated damage to liver DNA caused by the administration of tamoxifen to female Fischer F344/N rats or C57B1/6 or DBA/2 mice using 32P-postlabelling. Following the administration of tamoxifen for 7 days (45 mg/kg/day) and extraction of hepatic DNA, up to 7 radiolabelled adduct spots could be detected after PEI-cellulose chromatography of the 32P-labelled DNA digests. Tamoxifen caused a time-dependent increase in the level of adduct detected up to a value of at least 1 adduct/10(6) nucleotides after 7 days dosing. A dose response relationship was demonstrated over the range of 5-45 mg/kg/day (0.013-0.12 mmol/kg/day). On cessation of dosing there was a loss of adducts from the liver DNA. These adducts were not detected in DNA from vehicle-dosed controls or in DNA from kidney, lung, spleen, uterus or peripheral lymphocytes. Pyrrolidinotamoxifen caused a similar level of adduct formation as tamoxifen. In contrast, no significant adduct formation could be detected in liver DNA from rats given droloxifene or toremifene. Mice given tamoxifen (45 mg/kg/day for 4 days) showed levels of adducts in the liver which were 30-40% of those present in rats. Exposure of rat hepatocytes to tamoxifen in vitro, resulted in induction of unscheduled DNA synthesis, when preparations from rats which had been pretreated with tamoxifen in vivo were used. No such increase could be detected in hepatocytes from control rats, suggesting tamoxifen may induce enzymes responsible for its own activation. Tamoxifen induced a significant increase in micronucleus formation in a dose dependent manner in cultures of MCL-5 cells, a human cell line that expresses 5 different human cytochrome P450 isoenzymes, as well as epoxide hydrolase.
Carcinogenesis 1992 Dec
PMID:Genotoxic potential of tamoxifen and analogues in female Fischer F344/n rats, DBA/2 and C57BL/6 mice and in human MCL-5 cells. 147 24


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