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

Activated Harvey murine sarcoma virus ras genes were introduced into epidermal cells in vivo by direct application of retroviruses to mouse skin. Subsequent treatment with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced benign papillomas, some of which progressed to invasive carcinomas. Initiation with virus was irreversible for at least 4 months, since TPA treatment after this latency period produced papillomas within 4 weeks. Analysis of viral integration sites showed that carcinomas are clonal in origin. Both papillomas and carcinomas express virus-specific ras mRNA and the viral form of ras P21 protein. The results show that activated ras genes can replace chemical carcinogens in initiation of mouse skin carcinogenesis. This system presents a novel approach to in vivo analysis of the biological role of oncogenes in epithelial tumorigenesis.
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PMID:v-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis. 301 15

The isolation and characterization of oncogenes from human colon cancer and the recognition of their homology with the ras gene of the Harvey and Kirsten strain of murine sarcoma virus (MSV) led us to investigate the effect of exogenous MSV on 1,2 dimethylhydrazine (DMH)-induced colon carcinoma in rats. DMH, 20 mg base/kg, was injected weekly for 10 weeks into Sprague-Dawley rats. The Moloney murine sarcoma virus (MSV-M) was injected (200 focus-forming units) intraperitoneally into 15 rats 48 hours after the last DMH injection or in 12 rats before the first DMH injection. Controls consisted of 12 rats receiving 10 injections of DMH only, nine rats receiving MSV-M alone, and 10 untreated rats. All tumors induced were adenocarcinomas of the gastrointestinal tract, characteristically induced by DMH and not by MSV-M. In the late virus group there was an augmentation of colon tumor induction (mean, 2.2 versus 1.1 colon tumors/rat, p less than 0.05), and in the MSV pretreated group, there was also significant augmentation of colon tumor induction (mean, 2.4 versus 1.1 colon tumors/rat, p less than 0.005) when compared with rats treated with DMH alone. Rats treated with MSV-M alone and untreated rats had no tumors. This is the first study to suggest the importance of exogenous viral infection in chemically induced colonic carcinogenesis.
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PMID:The interaction of retrovirus and chemical carcinogen in experimental colon carcinogenesis. 302 10

Many human bronchial adenocarcinomas have been shown to contain an activated Ki-ras oncogene (Rodenhuis et al., N. Engl. J. Med. 317 929-935, 1987). To test the hypothesis that activated Ki-ras may be causally related to human bronchial carcinogenesis, v-Ki-ras oncogene was transferred into an established human bronchial epithelial cell line, BEAS-2B, by infection with Kirsten murine sarcoma virus (Ki-MSV) or by transfection with a plasmid containing the transforming region of Ki-MSV. These cells formed poorly differentiated adenocarcinomas in athymic nude mice. Cell lines established from these tumors expressed v-Ki-ras p21 protein and were highly tumorigenic. Whereas serum or transforming growth factor beta 1 induced the BEAS-2B cells at clonal density to undergo growth arrest and squamous differentiation, BEAS-2B cells containing activated ras genes were unaffected by transforming growth factor beta 1 and were mitogenically stimulated by serum.
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PMID:Human bronchial epithelial cells neoplastically transformed by v-Ki-ras: altered response to inducers of terminal squamous differentiation. 306 90

Two normal mortal human fibroblast cell strains were transformed into immortal cell lines, SUSM-1 and KMST-6, by treatment with 4-nitroquinoline 1-oxide (4NQO) and Co-60 gamma rays, respectively. These immortalized cell lines showed morphological changes of cells and remarkable chromosome aberrations, but neither of them grew in soft agar or formed tumors in nude mice. The immortal cell line, KMST-6, was then converted into neoplastic cells by treatment with Harvey murine sarcoma virus (Ha-MSV) or the c-Ha-ras oncogene derived from a human lung carcinoma. These neoplastically transformed cells acquired anchorage-independent growth potential and developed tumors when transplanted into nude mice. All the tumors grew progressively without regression until the animals died of tumors. In addition, the tumors were transplantable into other nude mice. Normal human fibroblasts, on the other hand, were not transformed into either immortal or tumorigenic cells by treatment with Ha-MSV or c-Ha-ras alone. Our present data indicate that (1) the chemical carcinogen, 4NQO, or gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to immortality, and (2) the ras gene played a role in the progression of the immortally transformed cells to more malignant cells showing anchorage-independent growth and tumorigenicity. In other words, the immortalization process of human cells seems to be a pivotal or rate-limiting step in the carcinogenesis of human cells.
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PMID:Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes. 314 Jul 12

The aim of this study was to investigate the possible influence of exposure to steroid hormones early in life on the susceptibility of animals as adults to chemical carcinogens. CBA male and female mice received a single subcutaneous injection of 0.5 mg testosterone propionate (TP) in olive oil within 24 h after birth. At the age of 2 months, neonatally androgenized and control mice started receiving weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH). By the end of the experiment, 90% of neonatally androgenized females treated with DMH developed uterine sarcoma against 9% in control females treated with DMH, this difference being attributed to the hyperoestrogenization of androgenized females. In neonatally androgenized males treated with DMH 79% developed pararenal sarcoma and 71% colon tumours versus 25 and 32% respectively of control males treated with DMH.
Carcinogenesis 1988 Nov
PMID:1,2-Dimethylhydrazine carcinogenesis in neonatally androgenized CBA mice. 318 Mar 31

As reported previously (Namba et al., 1985; Namba, 1985), normal human fibroblasts were transformed into immortal cells with abnormal karyotypes by Co-60 gamma-ray irradiation. These immortally transformed cells (KMST-6) showed no clonability in soft agar and were not tumorigenic. However, by treatment with Ha-ras oncogenes derived from a human lung carcinoma or Harvey murine sarcoma virus, the KMST-6 cells acquired elevated clonability in soft agar and transplantability in nude mice. All the tumors produced grew progressively without showing regression and killed the mice. The tumors were also serially transplantable into other mice. The Ha-ras oncogene alone did not convert normal human fibroblasts into either immortal or tumorigenic cells. Our current data suggest that gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to chromosome aberrations and immortality, and the Ha-ras oncogene played a role in the progression of the immortally transformed cell population to a neoplastic one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.
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PMID:Multi-step neoplastic transformation of normal human fibroblasts by Co-60 gamma rays and Ha-ras oncogenes. 328 50

Observations of cancer risk in irradiated human populations over time after exposure suggest that there are at least two, and perhaps more, very different patterns of temporal distribution of risk for radiation-induced cancer. The first, exemplified by bone sarcoma following therapeutic injection of 224Ra and chronic granulocytic leukemia in Japanese A-bomb survivors, is an early, wave-like pulse consisting of an increase in risk followed by a gradual decline back to baseline levels. The second, exemplified by breast cancer following a brief exposure to external gamma ray or X ray, and by lung cancer and stomach cancer in A-bomb survivors, is an increase in relative risk over about 10 years to a value which appears to remain constant over time thereafter. The first pattern suggests that tumor growth kinetics may play a central role in the temporal distribution of risk following exposure, while the second seems more consistent with multi-event models for carcinogenesis, in which radiation or some other cause of early events must be followed by one or more later events whose frequencies depend mainly on attained age. There are, however, other data that appear to conform to neither of the two models just mentioned. Influences of other cancer causes, like tobacco smoking, are potentially serious confounding factors in studies of induction period.
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PMID:Temporal distributions of risk for radiation-induced cancers. 331 74

After long-term feeding of a choline-devoid diet to rats, the authors analyzed rasK, rasH, and rasN transcripts and gene structure in livers and liver tumors. They controlled their analysis by studying cell lines derived from chemically induced hepatomas. Transcripts from all three genes were elevated in all tumors, but not in the livers from which they arose. The transcript elevations may represent an effect of active cell proliferation in the tumors. Clone HiHi-3, derived from the Kirsten murine sarcoma virus, detected a large number of hybridization bands, most of which were not part of the rasK-p21 gene. Most tumors had an altered band at 2.6 kb; some had other altered bands. No alterations were seen in liver DNA, and none of the cell lines showed the 2.6 kb band. At low stringency, a rasH probe, which contains a short segment of a similar viral sequence, also detected altered bands in tumors and a single treated liver. These changes in endogenous viral sequences of the rat genome appear to be characteristic of carcinogenesis by a choline-devoid diet.
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PMID:Analysis of ras genes and linked viral sequences in rat hepatocarcinogenesis. 331 28

Freshwater viviparous fishes of the genus Poeciliopsis are evaluated as a model for testing water-borne carcinogens. The unique property of this model lies in the clonal form of reproduction of some of these fishes. Interspecific hybrids between P.monacha and P.lucida occur in nature as all female 'species' which produce only female offspring and transmit the P.monacha genome intact as a single linkage group. Without sacrificing the integrity of the wild P.monacha genome, a naturally occurring 'hemi-clone' can be brought into the laboratory and rendered isogenic in the next generation by providing an inbred strain of P.lucida as the male parent. The genetic mechanism of P.monacha-lucida hybrids provides a tool for duplicating wild genomes from heterogeneous populations of these fishes for broad and continuous investigation. In the present study susceptibility to induction of liver tumors is compared in inbred strains of two species Poeciliopsis lucida and P.monacha, and among nine P.monacha-lucida hybrid clones exposed to diethylnitrosamine (DEN). Incidence of fish with liver tumors was significantly higher in P.lucida M61-31 (89.0%) than in P.monacha strains S68-4 (18.9%) and S68-5 (36.8%) and the nine hybrid clones of P.monacha-lucida wherein tumors occurred in a graded series (15.6 to 66.7%). Tumors were not found in any untreated fish reared as controls. The incidence of treated fish with large tumors (occupying more than one eighth of the liver) was significantly higher in P.lucida (72.7%) than in the P.monacha strains S68-4 (9.4%) and S68-5 (10.5%). The difference in frequencies of large tumors among the nine clones ranges from a low of 3.8% in M65-24 PCx to a high of 52.9% in M61-35 PCz. Hemangiopericytomas were induced in P.lucida and in five of the nine P.monacha-lucida clones; they were not found in either strain of P.monacha. Lymphosarcoma was induced only in P.monacha S68-5. An unclassified sarcoma was induced in both P.monacha strains and in two of the nine P.monacha-lucida clones, but not in P.lucida. The intrahepatic cholangiocarcinoma was the most frequent tumor type induced with DEN in this study. It occurred in all twelve genotypes, and with one exception, in the highest incidence. In contrast to a previous study wherein responses of different strains of P.lucida were within a narrow range, substantial differences exist among P.monacha genotypes.
Carcinogenesis 1988 Jun
PMID:Differences in response to a chemical carcinogen within species and clones of the livebearing fish, Poeciliopsis. 337 Jul 48

An affinity purified sheep IgG antibody to a 20 amino acid peptide from the carboxyterminal end of RasHa p21 was used to localize RasHa p21 on fixed tissue sections of Harvey sarcoma (HaSV) virus-infected mice by the avidin-biotin-peroxidase immunocytochemical technique. Control sera included immune sheep sera absorbed with the peptide, preimmune sheep sera and a goat polyclonal antibody to Rauscher leukemia virus p30. Neonatal BALB/c mice were injected with HaSV/Moloney leukemia virus (MoLV), MoLV alone or buffer. Short-term fixation in Bouin's fixative was found to be the most effective method for demonstrating p21 in fixed tissue sections. RasHa p21 was found in 5-80% of the induced sarcoma cells, depending on the tissue fixative and antibody dilution. The antigen was localized to the cell membrane and in the cytoplasm. Tumors induced by NIH 3T3 cells transformed with cellular Ha-ras oncogenes had less than 1% immunoreactive tumor cells. Splenic erythroblasts in HaSV-induced erythroblastosis contained membrane antigen as did some reticular cells in lymph nodes draining the sarcomas. Normal tissues of virus-inoculated mice, uninoculated controls or fetuses and selected naturally occurring or induced liver tumors of mice, chemically induced skin tumors of mice, N-nitrosomethylurea-induced mammary tumors of rats, and naturally occurring tumors of F344/NCr rats did not contain immunoreactive p21. Thus, with the use of affinity purified IgG sheep polyclonal antibody to a peptide in RasHa p21, we were able to demonstrate RasHa p21 in tumors and other cells. The degree of immunoreactivity was related to the expected level of p21 expression.
Carcinogenesis 1986 Apr
PMID:Immunocytochemical localization of RasHa p21 in normal and neoplastic cells in fixed tissue sections from Harvey sarcoma virus-infected mice. 351 33


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