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

To investigate the role of carcinogenesis in determining the response of tumors to anticancer drugs, we have used the in vivo model of multistage carcinogenesis of the mouse skin. Mice were initiated with Harvey murine sarcoma virus or single and repeated applications of dimethylbenzanthracene (DMBA). The papillomas which developed as a result of these initiation protocols were monitored quantitatively for their response to the anticancer drug doxorubicin. A single dose of 10 mg/kg doxorubicin is relatively inefficient at reducing the frequency of papillomas arising as a result of either single or repeated applications of the chemical DMBA. However, virally initiated papillomas are sensitive to the single 10-mg/kg dose of doxorubicin and are reduced in frequency by greater than 80%. Repeat treatment with four doses of 5 mg/kg doxorubicin over a 4-week period also reveals differences in the responses of the papillomas to doxorubicin. As with the single dose of doxorubicin, papillomas initiated with multiple applications of DMBA showed only a limited response to four 5-mg/kg doses of doxorubicin. In comparison both the virally initiated and the single DMBA initiated papillomas responded to the four doses of doxorubicin and are reduced in frequency by about 80%. These data show that the response of papillomas to doxorubicin is related to the initiating event. Papillomas derived by viral initiation are most sensitive to doxorubicin while increasing the level of exposure to the chemical carcinogen DMBA increases the proportion of papillomas which do not respond to treatment with doxorubicin. There was no obvious relationship between the method of initiation or the treatment of the mice with doxorubicin and the levels of P-glycoprotein expression observed in the papillomas. All the papillomas expressed detectable levels of P-glycoprotein approaching that of the multidrug resistant cell line, CHRC5.
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PMID:Response of mouse skin tumors to doxorubicin is dependent on carcinogen exposure. 197 37

Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a "collision" tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months (median 40 months). The IORT dose range associated with tumor development was 20-35 Gy (median 30 Gy). The carcinogenesis capability of single fraction, high dose radiation in animals is discussed, as are the implications of these data for continued research and clinical usage of IORT in the treatment of humans.
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PMID:Tumor induction following intraoperative radiotherapy: late results of the National Cancer Institute canine trials. 212 Jan 59

To investigate genetic and sex factors in the local tumorigenesis by 7,12-dimethylbenz(alpha)anthracene (DMBA) in the mammary gland, both males and females of two different inbred strains of rats, Wistar/Furth (WF) and Copenhagen (COP), were subjected to dusting with approximately 1 mg of DMBA powder directly onto the exposed inguinal mammary tissue at 30 days of age. Locally growing tumors to 2 cm in mean diameter were harvested during 28 weeks after the carcinogen application. The incidence of macroscopic tumors of mammary origin was 100% in 15 WF females, 19% in 16 WF males, 85% in 20 COP females, and 74% in 19 COP males. Histologic pictures indicated the carcinomatous pattern composing mainly of differentiated adenocarcinoma of ductular cells in 12 tumors (80%) from WF females but not in any tumors from the other groups. On the other hand, they showed the sarcomatous pattern characterized by undifferentiated sarcoma of stromal cells in 2 tumors (13%) from WF females, 3 tumors (19%) from WF males, 16 tumors (80%) from COP females, and 14 tumors (74%) from COP males. The other 2 tumors from 1 WF and 1 COP females revealed the carcinosarcomatous pattern. Therefore, mammary ductular cells of WF are highly susceptible to DMBA and may be modified by sex factors in their carcinogenesis. Mammary stromal cells of COP are extremely susceptible to DMBA independently of sex factors.
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PMID:Strain difference in neoplastic response to DMBA powder dusted onto mammary tissues between Wistar/Furth and Copenhagen strains of rats. 212 11

In keeping with the multistep development of human cancer in vivo, a stepwise approach to neoplastic transformation in vitro presents a reasonable strategy. We have recently developed an in vitro multistep model suitable for the study of human epithelial cell carcinogenesis. Upon infection with the adenovirus 12-simian virus 40 hybrid virus, primary human epidermal keratinocytes acquired an indefinite life span in culture but did not undergo malignant conversion. Subsequent addition of Kirsten murine sarcoma virus and human ras oncogene or chemical carcinogens (N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline 1-oxide) to these cells induced morphological alterations and the acquisition of neoplastic properties. Subsequently it was found that this line could be transformed neoplastically by a variety of retrovirus-containing H-ras, bas, fes, fms, erbB, and src oncogenes. In addition, we found that the immortalized human epidermal keratinocyte (RHEK-1) line can be transformed neoplastically by exposure to ionizing radiation. Thus, this in vitro system may be useful in studying the interaction of a variety of carcinogenic agents and human epithelial cells. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of viruses, oncogenes, chemical carcinogens, or X-ray irradiation and support a multistep process for neoplastic conversion.
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PMID:Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis. 216 63

The study was concerned with the evaluation of effect of the extract of a human fetal organ, the umbilical cord, on development and growth of such transplantable tumors as Ehrlich's ascites tumor, sarcoma 37, sarcoma 180 and Zajdela's hepatoma as well as of dimethylbenzanthracene- and benzo(a)pyrene-induced cancer. In a subgroup of animals who had been vaccinated once or twice prior to inoculation of cells, a significant inhibition of growth of tumors of all the histologies except sarcoma 180 was observed alongside with a decrease in tumor incidence and partial resorption of ascitic fluid. Preliminary vaccination of rats interfered with dimethylbenzanthracene- and benzo(a)pyrene-induced carcinogenesis reducing tumor incidence and assuring longer latent period and slower progression of cancer.
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PMID:[The antitumor effect of an extract of human umbilical cord]. 221 39

Repair of X-ray-induced single-strand breaks of DNA was studied in vitro using an exonuclease purified from mouse ascites sarcoma (SR-C3H/He) cells. X-ray-dose-dependent unscheduled DNA synthesis was primed by the exonuclease. Repair of X-ray-induced single-strand breaks in pUC19 plasmid DNA was demonstrated by agarose gel electrophoresis after incubating the damaged DNA with the exonuclease, DNA polymerase (Klenow fragment of DNA polymerase I or DNA polymerase beta purified from SR-C3H/He cells), four deoxynucleoside triphosphates, ATP and DNA ligase (T4 DNA ligase or DNA ligase I purified from calf thymus). The present results suggested that the exonuclease is involved in the initiation of repair of X-ray-induced single-strand breaks in removing 3' ends of X-ray-damaged DNA.
Carcinogenesis 1990 Jul
PMID:Repair of X-ray-induced single-strand breaks by a cell-free system. 237 79

Bleomycin-induced, unscheduled DNA synthesis (UDS) in Triton X-100-permeabilized mouse ascites sarcoma cells was enhanced 2- to 5-fold by addition of ribonucleoside triphosphates at 0.2-2.0 mM and 1.5- to 3-fold by addition of ferrous ions at 10 microM. Sensitivity to deferoxamine, a specific iron chelator, suggested that iron was essential to nucleotide-enhanced, bleomycin-induced UDS. Enhancement by nucleotides was not attributed to iron impurities in the nucleotide preparations, because ferrous ions did not substitute for nucleotides, but nucleotides further enhanced bleomycin-induced UDS which was maximally stimulated by the optimal concentration of ferrous ions. The effects of nucleotides and ferrous ions on bleomycin-induced UDS were thought to be due to increased bleomycin-induced DNA damage rather than enhanced DNA synthesis. The results suggest that pharmacological action of bleomycin is affected by the concentrations of nucleotides as well as ferrous ions.
Carcinogenesis 1985 Jun
PMID:Effects of nucleoside triphosphates and ferrous ions on bleomycin-induced unscheduled DNA synthesis. 240 74

Human epidermal cells, despite being 'immortalized' or 'transformed' by combinations of either oncogenic virus (SV40, adenovirus 12 or Kirsten murine sarcoma virus) or chemical carcinogen (N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide) exhibited similar keratins (although quantitatively reduced) to that of control cells when grown in vitro. However, athymic nude mouse tumors derived from such cells exhibited suppression of the 52, 56 and 58 kd (basic type II) keratins and a predominance of small-sized (40-48 or 50 kd) (acidic type I) keratins. The synthesis of these specific keratins was resumed following re-establishment of cell lines in culture. These results suggest that the changes in keratin protein profiles frequently exhibited by human carcinomas represent a component of the pleomorphic transformed phenotype which can be uncoupled from neoplastic growth.
Carcinogenesis 1986 Jan
PMID:Keratin expression of both chemically and virally transformed human epidermal keratinocytes during the process of neoplastic conversion. 241 37

Studies of the mutagenic action required for specific chemicals to produce benign or malignant tumours suggest that in mouse skin at least two genetic events occur before carcinoma formation. The isolation of an activated form of the c-rasH gene from skin papillomas has provided evidence that this gene may be a target for the first mutation, which could constitute the initiating mutation in skin carcinogenesis. In vitro studies indicate that the v-rasH gene of Harvey murine sarcoma virus (Ha-MSV), a replication-defective transforming retrovirus, could impart a conditional initiated phenotype on cultured keratinocytes by blocking their ability to differentiate terminally and arresting them in a late basal cell stage of maturation. We now show that when the Ha-MSV v-rasH gene is introduced into cultured keratinocytes by a defective retroviral vector, skin grafts constructed with cells carrying the mutated ras oncogene produce papillomas on athymic nude mouse recipients. Furthermore, the expression of the exogenous oncogene seems to be regulated at the transcriptional level in the differentiated portions of the benign tumour.
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PMID:An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissue. 243 Jan 89

Effects of ATP and some other nucleotides (AMP, ADP, CTP, GTP, UTP and dATP) on reparative DNA synthesis and repair patch ligation in bleomycin-pretreated permeable mouse sarcoma cells were studied. Reparative DNA synthesis was significantly stimulated by 2.5 mM ATP, ADP or dATP. The stimulation was observed on both DNA polymerase alpha- and beta-dependent reparative DNA synthesis. ATP concentration required for repair patch ligation was much lower than that required for the stimulation of reparative DNA synthesis. An apparent Km value for ATP of the repair patch ligation was about 40 microM. ADP supported repair patch ligation after being converted into ATP by adenylate kinase in permeable cells.
Carcinogenesis 1987 Oct
PMID:Effects of ATP and other nucleotides on DNA repair synthesis in bleomycin-pretreated permeable mouse sarcoma cells. 244 62


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