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

To reveal the relationship between teratogenesis and carcinogenesis, the author studied brain blastomogenesis features against the background of the development of deformities induced by the combined transplacental effect of NMU and NEU. To induce brain defects such as microcephaly NMU was injected on the 15th day, whereas to induce cerebellar defects- on the 21st day of embryogenesis. Moreover, at the 13th or 17th day NEU was additionally injected, which is found to be highly effective for inducing brain tumors. It was found that in NMU exposure (at the 15th day) until NEU exposure (at the 17th day of embryogenesis) no reliable decrease in brain tumor occurrence was noted, compared with that if only NEU was employed. In the reverse sequence, i. e. first the exposure to NEU (at the 13th day) and then to NMU (at the 15th day) the occurrence of tumors located in cerebral hemisphers was 3 times less. It is assumed that cytotoxic effect of NMU leading to microcephaly is likely to cause the death of a considerable amount of cell population previously transformed.
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PMID:[Combined transplacental carcinogenic action of N-nitrosomethylurea (NMU) and N-nitrosoethylurea (NEU) in rats]. 65 72

Carcinogenic metal compounds, with the exception of chromium(VI), have been found to be poorly mutagenic in both prokaryotic and mammalian cell mutagenesis assays, yet they are clearly clastogenic (Hansen and Stern, 1984). Thus, the role of metals as initiators in carcinogenesis has been difficult to delineate. In an effort to develop a model system capable of assaying DNA damage caused by carcinogenic metals, we have investigated the role of NiCl2, CdCl2, Na2CrO4, and NMU in a murine sarcoma virus-infected mammalian cell line in which expression of the retroviral v-mos gene is growth-temperature regulated. This cell line, designated 6m2, contains a single-copy, stably integrated, mutant Moloney murine sarcoma virus DNA (designated MuSVts110) and is temperature sensitive for morphological transformation due to a conditionally defective viral RNA-splicing event that in turn regulates expression of the viral transforming gene. Mutations affecting the viral DNA in 6m2 cells can be detected if these alterations lead to changes in the structure or expression of the transforming protein encoded by the MuSVts110 v-mos gene. Analysis of the viral proteins from 6m2 'revertant' cell lines (as defined by reversion to the transformed phenotype at all growth temperatures) selected after treatment with the above agents showed that NiCl2, NMU, and Na2CrO4 each induced a different yet specific type of mutation. NiCl2 and NMU each altered the temperature sensitivity of viral RNA splicing, possibly due to base substitution mutations, but did so to distinctly different extents. Na2CrO4 affected the structure of the viral proteins by inducing what appear to be short frameshift mutations that resulted in the temperature-dependent translation of a novel virus-encoded transforming protein, P100gag-mos. CdCl2 also induced frameshift mutations but, in one case, induced a mutation which may result from a deletion of about 300 bases within the MuSVts110 DNA.
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PMID:Analysis of metal-induced mutations altering the expression or structure of a retroviral gene in a mammalian cell line. 283 50

A single treatment of adult animals with the potent carcinogen NMU was known to induce tumours in a wide variety of organs, with the notable exception of liver. Administration of NMU after partial hepatectomy gave rise to the first liver cell adenomata ever observed in rats due to this carcinogen. The tumours were induced when NMU was given during the period of increased DNA synthesis but not when given early in the pre-replicative period. Although tumours were induced in other organs, the incidence of these did not correlate with the timing of NMU administration. It is suggested that replication of damaged DNA may be a relevant event in carcinogenesis.
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PMID:Induction of liver cell adenomata in the rat by a single treatment with N-methyl-N-nitrosourea given at various times after partial hepatectomy. 461 56

Three-month-old male and 3-month-old female LIO rats as well as 25-month-old males and 3-month-old females were mated and at the age of 3 months their progeny were exposed to a single intravenous injection of N-nitrosomethylurea (MNU) at the dose of 20 mg/kg of body weight or solvent. Animals were under observation during 18 months after injection of the carcinogen. There was no significant difference in spontaneous tumor incidence between progeny of young and old male rats. At the same time, the susceptibility to the carcinogenic effect of NMU in the male and female progeny of old males was slightly but significantly increased in comparison to the progeny of young males. Mesenchymal kidney tumors were discovered in the NMU-treated male progeny of old males but not in the male progeny of young male rats. In females, the incidence of mesenchymal kidney tumors in the NMU-treated progeny of young and old males was 7% and 20%, respectively, and the mean survival times of these tumor-bearing rats was 4 months shorter in the last group. The data obtained are in agreement with the observation on germ-line transgeneration transmission of predisposition to carcinogenesis.
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PMID:N-nitrosomethylurea-induced carcinogenesis in the progeny of male rats of different ages. 786 77

The breast cancer gene BRCA1 has previously been cloned from both human and mouse. We cloned a fragment of the rat Brca1 homologue in order to map it and explore its biological function. Partial cDNA fragments of the rat Brca1 homologue were isolated by RT-PCR. Sequence analysis revealed that the RING-finger domain is well conserved among rat, mouse and human. Rat Brca1 mRNA was expressed in most tissues studied with the highest level in testis, consistent with studies in human and mouse. Next, intron 6-containing DNA fragments were amplified by PCR from WKY and WF rat strains. The splicing sites between exon 6 and exon 7 are conserved between rat and human. Partial sequencing of the rat Brca1 intron 6 revealed a polymorphism of a pentanucleotide TTTTG repeat between the WKY and WF strains. With this intragenic microsatellite marker, we were able to map precisely the rat Brca1 gene to chromosome 10 using a genetic linkage study of (WKY x WF)F1 x WF backcross rats. Brca1 cosegregates with marker BAND3A, and is flanked by R5123 and R5842. Using this polymorphic marker, we also investigated the loss of heterozygosity (LOH) of the Brca1 microsatellite marker in carcinogen- or radiation-induced mammary carcinomas in (WF x F344)F1 female rats. No LOH or somatic microsatellite instability was detected in 18 DMBA-induced tumors studied. Only one LOH of the F344 allele was observed in 26 radiation-induced tumors tested. Ribonuclease protection assays demonstrated that Brca1 mRNA levels are similar in normal rat mammary glands and mammary carcinomas of various etiologies, including those induced by DMBA, NMU, activated-neu and activated-ras oncogenes.
Carcinogenesis 1996 Aug
PMID:Cloning, genetic mapping and expression studies of the rat Brca1 gene. 876 10

Outbred female rats from the age of 1 month were kept at rooms with 12 h light: 12 h dark (LD), 24 h light (LL) and 24 h dark (DD) regimens and 2 weeks later were exposed to 3 weekly i.v. injections of NMU at the dose of 50 mg/kg and starting in 2 days after first NMU administration-to variable or static magnetic fields (VMF and SMF). Exposure to LL regimen significantly promoted whereas the exposure to DD regimen significantly inhibited NMU-induced mammary carcinogenesis. RIA of serum samples from rats maintained under different light regimens has shown that exposure to LL followed by decrease of melatonin level and increase of prolactin level at all of modifying factors (NMU, VMF, SMF). Surgical light deprivation inhibits NMU-indiced mammary carcinogenesis in female rats. The primary role of pineal function in the modifying effects of light/dark regimens and electromagnetic fields on mammary carcinogenesis are suggested.
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PMID:[Effect of the light regime and electromagnetic fields on mammary carcinogenesis in female rats]. 896 82

Individual genetically determined susceptibility to cancer as well as acquired epigenetic and genetic organ specific alterations are important considerations in choosing target populations for chemopreventive trials. These individual epigenetic and genetic alterations can also serve as potential biomarkers for chemoprevention clinical trials. In order to model these potential markers for chemoprevention investigations, we are examining a series of interrelated rat models. Inbred rats vary in their susceptibility to mammary cancer induction by environmental agents. For example, the WF strain is highly susceptible to chemically induced mammary cancer while the Cop rat is almost completely resistant. The F344 is intermediate in susceptibility to chemically induced mammary cancer. These differential susceptibilities are inherited in a dominant pattern. For example, resistance is due to the inheritance of Mcs gene(s) which likely act by altering the differentiation lineage of mammary epithelial cells. As tumors form in the mammary glands of these rats, they acquire additional epigenetic and genetic alterations. Epigenetic initiation is a very frequent cellular event following carcinogen exposure which may predispose cells to genetic change including allelic imbalance. For example, following a standard dose of NMU or DMBA over 1% of cells are epigenetically initiated. During the carcinogenesis process, initiated cells may acquire genetic change such as oncogene activation and allelic imbalance. Interestingly, the pattern of allelic imbalance appears to be an inherited trait. For example, a non-random loss of heterozygosity (LOH) in rat chromosome 1 following DMBA only occurs in certain strains, such as Cop rats. Interestingly this change does not occur following initiation by ionizing radiation. It will thus be important to identify these epigenetic and genetic events which underlie mammary carcinogenesis as well as determine their patterns of inherited predisposition and temporal occurrence. Such knowledge is critical if we are to develop new molecular markers for chemoprevention trials.
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PMID:Inherited susceptibility and acquired allelic imbalance in rat mammary carcinogenesis. 902 96

The purpose of this work was to determine the hormone dependence of mammary tumors induced in Sprague-Dawley rats by three intraperitoneal injections of N-nitroso-N-methylurea at 50, 80, and 110 days of age. Two experimental designs were carried out: (a) Ten days before the first NMU injection, 130 rats were divided into 13 batches and randomly assigned to the following treatments: control, ovariectomy (OVX), tamoxifen (TAM), bromocriptine (BROM), haloperidol (HAL), estradiol (E2), progesterone (Pg), OVX + BROM, TAM + BROM, OVX + HAL, TAM + HAL, OVX + TAM, and E2 + BROM. After 150 days of treatment the following growth parameters were determined: latency period (LP), mean tumor number per rat (n/t), and tumor incidence (TI). LP was significantly increased (p < 0.05) only by Pg and TAM + BROM. The n/t was significantly decreased (p < 0.05) by all treatments except HAL. TI was significantly reduced by OVX, TAM, BROM, and their combinations, (b) Rats bearing ip-NMU-induced mammary tumors were divided into 7 batches and assigned to the following treatments: control, OVX, TAM, BROM, HAL, OVX + BROM, and TAM + BROM. Tumor growth was assessed up to 60 days of treatment; only OVX, TAM and their combination with BROM were able to produce tumor regression. These results support the essential role of E2 and prolactin in the promotion stage of carcinogenesis. However, for established tumors, growth becomes more independent from hormone influence, in particular from prolactin deprivation. We conclude that this model seems suitable for studying the mechanisms underlying the evasion of hormonal control of tumor growth.
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PMID:Hormone dependence of mammary tumors induced in rats by intraperitoneal NMU injection. 902 85

A significant role of chemical, physical and hormonal factors modifying transplacental carcinogenesis has been established. It was found that, in tumors induced during gestation by carcinogenic agent treatment, ras oncogenes are activated due to their point mutation. The progeny of male animals exposed to radiation before mating with intact females prove to be more susceptible to such carcinogenic promoters as urethane and TPA than controls while the descendants of older males and young females are more susceptible to NMU treatment than those of young males and females. Convincing evidence of selective DNA damage being relevant to initiation of carcinogenesis was first obtained in experiments involving the use of a synthetic analog of thymidine 5-bromodesoxyuridine. Experimental treatment with carcinogenic agents and tumor promoters at different age has demonstrated age-related accumulation in different tissues of cells which have been randomly exposed to carcinogenic substances and, as a result, are pass at least one stage before complete malignant transformation. It is also assumed that such partially transformed cells are exposed to the carcinogenic effect which increases in proportion to age. Significant differences in age-related changes in the sensitivity of different tissues to the action of different carcinogens have been identified. A direct correlation between the pattern of aging delay in a population affected by a certain geroprotector and its influence on neoplasm development was established on the basis of an evaluation of the evidence on tumor incidence in experimental animals following geroprotector administration.
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PMID:[Carcinogenesis and ontogenesis: chief trends and results of investigations]. 913 95

Recently a great variability of various mouse and rat strains in the sensitivity for mammary tumors induction by means of physical (ionizing radiation) or chemical (mostly 7,12-dimethylbenz/a/anthracene, DMBA and N-methyl-N-nitrosourea, NMU) initiating agents was noted. The categorization into four groups was recommended in rats; the first group with high sensitivity (the incidence of tumors practically 100%, the frequency of tumors per entire treated group 2.0), the second with average type of sensitivity (incidence below 100%, frequency between 1.0-2.0), the third with low sensitivity (frequency 0.3-.4) and the fourth with zero sensitivity as the response to single standard dose of DMBA. After initial observations we decided to analyze the sensitivity to mammary carcinogenesis in the female rats of Wistar:Han strain, used frequently in central European region. Twenty mg of DMBA by gavage as single dose, or three-times 10 mg by gavage as repeated consecutive doses in three-day intervals, or 30 mg/kg b.w. of NMU intraperitoneally were administered, always between 50-55 postnatal days (single doses) or between 50-60 days (repeated doses of DMBA). The average incidence of mammary tumors did not exceed 10% and the entire group tumor frequency was about 0.1 for both carcinogens used. The data allowed us to indicate the female Wistar:Han rats as animals with "very low" sensitivity for the initiation of mammary tumors by single dose of DMBA or NMU; being in this way very close to the insensitive strains. The fact of "sensitivity" improvement to higher range after repeated doses of DMBA indicated a non-genetic background of the changed sensitivity. Our results support the need to use more then one rat strain for initiation of mammary carcinogenesis, and for assessing the bright range of the biological response. In this situation the concept of "multi-strain" assay seems to be the optimal.
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PMID:Very low sensitivity of Wistar:Han female rats to chemocarcinogens in mammary carcinogenesis induction. 1021 Jan 11


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