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

Many lines of evidence exist associating herpes simplex virus (HSV) with the development of carcinoma, but much of this evidence is anecdotal or associative in nature and does not prove a cause and effect. The purpose of this research was to investigate the oncogenic potential of HSV type 2 (HSV-2) in vivo. A mouse model for lip carcinogenesis was designed to combine HSV-2 infection, u.v. exposure and tetradecanoyl-phorbol-acetate (TPA) application. HSV-2 inoculation on to abraded mouse lips was capable of causing vesicular ulcerative lesions which healed completely after 10 to 14 days. Ultraviolet irradiation of the HSV lesion site daily for 6 min at 42 ergs/mm2/s on days 3 to 6 post-infection caused hyperkeratosis, acanthosis and dysplasia to develop in several lips; while the same u.v. exposure by itself failed to alter the histologic appearance. The addition to repeated TPA application to the HSV+ u.v. regimen promoted tumour emergence. Thirty-two of 156 Balb/c mice developed tumours. Although the majority were papillomas, six were squamous cell carcinomas. These tumour-bearing mice had increased HSV-specific antibody titres. HSV antigens were shown to be present in outgrowths from explanted tumours as well as in tumour biopsies by immunoperoxidase staining with HSV-specific antisera. It is suggested that the in vivo u.v.-irradiated HSV acted as the inducer and TPA as the promoter, analogous to the classical two-stage carcinogenesis model.
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PMID:Conversion of herpetic lesions to malignancy by ultraviolet exposure and promoter application. 627 Feb 65

The effects of the comutagen norharman on herpes simplex virus type 2 growth transformation was studied in 3T3 cells. Pre-exposure but not post-exposure of the cells to 0.5 to 10 micrograms of norharman per ml of cell culture media resulted in a nearly three-fold enhancement in transforming activity. These results suggest that certain environmental chemicals may interact with cells creating an increased possibility of transformation by herpes viruses.
Carcinogenesis 1982
PMID:Chemical interactions with herpes simplex type 2 virus: enhancement of transformation by norharman. 628 1

Quantitative assays for the morphological transformation of 3T3 Swiss mouse cells by herpes simplex type 2 virus (HSV-2) were employed to examine the effect on cell transformation of chemical carcinogens and pro-carcinogens. The carcinogens tested were N-methyl-N'-nitro-N-nitrosoguanidine, quinacrine mustard, N-nitrosomethyl urea, urethane, and benzene. The pro-carcinogens tested were N-nitrosodimethylamine, 3-methylcholanthrene, benzo[a]pyrene, and p-dimethylaminoazobenzene. Exposure of the cells to the chemical compound and to the virus resulted in enhancement of transformation when compared to that observed with chemical or virus alone. Enhancement of transformation occurred in cells treated with all of these compounds. In general, enhancement occurred regardless of whether the cells were pre-exposed to the carcinogen or pre-infected with virus. These results are suggestive of combined herpes virus and chemical effects on cells resulting in increased risk of oncogenic transformation.
Carcinogenesis 1982
PMID:Chemical interactions with herpes simplex type 2 virus: enhancement of transformation by selected chemical carcinogens and pro-carcinogens. 629 37

Herpes simplex virus is a common cause of infection of the female genital tract. The infection can be diagnosed by the cytopathologist from the appearances of multinucleate giant cells in Papanicolaou smears. The cytological diagnosis of this infection is of value to the gynecologist in identifying subclinical infection and in confirming clinically suspicious disease. The validity of the cytological diagnosis can be established by virus isolation or electron microscopy. Although other infections of the female genital tract such as wart virus infection, cytomegalovirus infection, and chlamydial infection can be detected by cytological methods, the reliability of the cytological approach has yet to be established. Nevertheless, cytology has provided a powerful stimulus for research into the prevalence of wart virus infection of the cervix, which has been shown to be much more common than was previously supposed, and may be a factor in cervical carcinogenesis. Cytological examination of smears of urinary sediment has proven to be a reliable method of detecting human polyomavirus excretion in pregnancy. Active infection of the urinary tract occurs in 3.2% of pregnant women who represent an "at risk group" with altered immunological function.
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PMID:Cytological diagnosis of virus-infected cells in cervical smears. Value in gynecologic and obstetric practice. 629 74

Cytomegalovirus (CMV) was isolated in cell cultures derived from 2 of 11 nasopharyngeal carcinoma (NPC) biopsy specimens from North African patients. All these cases were Epstein-Barr virus (EBV)-associated NPC. Morphologic cytopathic changes and viral replication not associated with EBV were observed after 2 months in culture. Virus identification was achieved by immunofluorescence studies, and cell culture antigens were tested by the use of complement fixation and indirect hemagglutination. All these NPC patients had been infected by herpes simplex virus, varicella-zoster virus, and CMV, but the antibody titers determined by complement fixation and immunofluorescence were normal. CMV, which is not associated with this cancer, could nevertheless favor carcinogenesis in facilitating fusion between epithelial cells and EBV-positive lymphocytes.
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PMID:Cytomegalovirus isolations from cell cultures derived from Epstein-Barr virus-associated nasopharyngeal carcinoma. 630 25

Primary epidermal cells from AKR, BALB/c, CD-1, and SENCAR mice, listed in order of least to most sensitive to epidermal carcinogenesis by initiation and promotion protocols, were found to be equally competent to "reactivate" herpes simplex virus type 1 irradiated by germicidal ultraviolet radiation. Nontumorigenic BALB/c epidermal cell lines selected in vitro for resistance to terminal differentiation after in vivo or in vitro treatment with initiating doses of carcinogens showed virus survival curves similar to those of primary cells. Similarly, primary cultures which were allowed to grow to confluency following a single treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (100 ng/ml) retained normal host cell reactivation. Host cell reactivation studies with mouse dermal fibroblasts could not be done because of the failure of the herpes simplex virus to infect these cells and produce plaques. These results demonstrate that survival of ultraviolet light-damaged virus in primary epidermal cells in culture is unrelated to whether the cells are derived from mice sensitive or resistant to epidermal carcinogenesis. Furthermore, virus survival is not changed by tumor promoter treatment or by treatment with initiating doses of carcinogens which results in differentiation-resistant cells.
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PMID:Host cell reactivation studies with epidermal cells of mice sensitive and resistant to carcinogenesis. 631 86

The purpose of this investigation was to determine whether cells transformed by herpes simplex virus type 2 (HSV-2) can be stimulated to synthesize prostaglandins (PG). Stimulation was determined by measuring the release of PG into overlay fluids from cell monolayers prelabeled with [3H]arachidonic acid. Results showed that Ca2+ ionophore A-23187 markedly stimulated arachidonic acid release starting 30 min after treatment of HSV-2-transformed and nontransformed rat embryo fibroblast cells. However, only HSV-2-transformed cells were stimulated in production of PG. HSV-2-transformed, nontumorigenic, rat embryo fibroblast, line G, clone 2.0 cells synthesize nearly equal amounts of prostaglandin E2 (PGE2) and prostaglandin F2 alpha, while tumor (rat fibrosarcoma) cells synthesize primarily PGE2. Stimulation of PGE2 synthesis by Ca2+ ionophore A-23187 or 12-O-tetradecanoyl-phorbol-13-acetate decreased as rat fibrosarcoma cells were serially passaged in tissue culture. At low passage of parental rat fibrosarcoma cells, four distinct morphological clonal cell lines were isolated, which varied markedly in their capacity to be stimulated in PG synthesis by 12-O-tetradecanoyl-phorbol-13-acetate. There was correlation between the capacity of clone 1 cells to be stimulated in PGE2 synthesis by serum alone and capacity of the tumors produced by the clone 1 cells to metastasize to the lungs of syngeneic tumor-bearing rats. In summary, cell transformation by HSV-2 appears to be essential for stimulation of PG synthesis in cells. The capacity to be stimulated in arachidonic acid metabolism and PG synthesis may be important in the process of carcinogenesis by a putative human cancer virus.
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PMID:Calcium ionophore A-23187 and 12-O-tetradecanoyl-phorbol-13-acetate stimulation of prostaglandin synthesis in herpes simplex virus type 2-transformed rat cells. 632 82

Carcinogen treatment of cultured mammalian cells prior to infection with u.v.-irradiated virus results in enhanced virus survival and mutagenesis suggesting the induction of SOS-type processes. In this paper, we report the development of a primary rat hepatocyte culture system to investigate cellular responses to DNA damage which may be relevant to hepatocarcinogenesis in vivo. We have obtained data demonstrating that enhanced reactivation of u.v.-irradiated Herpes simplex virus type 1 (HSV-1) occurs in hepatocytes irradiated with u.v. Cultured hepatocytes were pretreated with u.v. at the time of enhanced DNA synthesis. These treatments caused an inhibition followed by a recovery of DNA synthesis. At various times after pretreatment, the hepatocytes were infected with control or u.v.-irradiated HSV-1 at low multiplicity, and virus survival was measured by direct plaque assay. U.v.-irradiated HSV-1 exhibited the expected two-component survival curve in control or u.v. pretreated hepatocytes. The magnitude of enhanced reactivation of HSV-1 was dependent on the u.v. dose to the hepatocytes, the time of infection following u.v. pretreatment, and the level of DNA synthesis at the time of pretreatment. These results suggest that u.v. treatment of rat hepatocytes causes the induction of SOS-type functions that may have a role in the initiation of hepatocarcinogenesis.
Carcinogenesis 1984 Apr
PMID:U.v.-enhanced reactivation of u.v.-irradiated herpes virus by primary cultures of rat hepatocytes. 632 50

SENCAR mice are markedly more susceptible to two-stage skin carcinogenesis than BALB/c mice. Studies were carried out to elucidate the basis for this sensitivity. It is not related to differences in the metabolism of polycyclic aromatic hydrocarbons (DiGiovanni et al., 1980) but appears to be determined by the target tissue, since when SENCAR skin was grafted onto nude mice they developed papillomas at a high frequency after initiation and promotion, whereas after grafting of BALB/c skin, no tumours developed. DNA repair capacity was studied in SENCAR and BALB/c epidermal cells in culture. Host cell reactivation, utilizing ultra-violet light-irradiated herpes simplex virus, was similar in cells of the two strains. SENCAR cells have a greater binding capacity for epidermal growth factor than BALB/c cells; however, the increased binding in response to retinoic acid and the rapid decrease after exposure to phorbol esters are similar in the two strains. Spontaneous expression of endogenous proviral DNA sequences for xenotropic-type C RNA viruses occurs more readily in BALB/c epidermal cells than in those of SENCAR. The frequency of spontaneous differentiation-resistant foci in vitro (Kulesz-Martin et al., 1980) is greater in SENCAR than in BALB/c epidermal cells. These results suggest that susceptibility for skin carcinogenesis in SENCAR mice is determined by the target tissue itself and has no clear relation to DNA excision repair, endogenous virus complement or epidermal growth factor receptors.
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PMID:Susceptibility determinants for mouse epidermal carcinogenesis. 698 14

The replacement of functional genes into cells that lack genes or have mutant genes is the basis of gene therapy. In cancer, where cells often have multiple genetic defects, the replacement of critical genes may suffice to suppress cell growth or induce cell death. The high frequency of mutations of the p53 tumor-suppressor gene in human cancers, including primary brain tumors, suggests that p53 plays a critical role in carcinogenesis and tumor progression. We report the successful transfer of the wild-type p53 gene using a defective herpes simplex viral vector into a human medulloblastoma cell line containing a mutant copy of p53. Upon gene transfer, we detected novel expression of wild-type p53 protein in the cells. In addition, the p53 protein was functionally active, since gene transfer resulted in increased levels of mdm2 proteins and induced cell cycle arrest of the majority of transduced cells. To our knowledge, this is the first report of the use of this vector system to carry wild-type p53. We conclude that defective herpes simplex viral vectors can transfer and express p53 in human primary brain tumor cells in vitro, restoring wild-type p53 tumor-suppressor functions.
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PMID:Gene transfer of wild-type p53 results in restoration of tumor-suppressor function in a medulloblastoma cell line. 764 54


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