Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potent epoxide hydrase inhibitor, 1,1,1-trichloro-2,3-propene oxide (TCPO), enhanced the tumor-initiating ability of benzo[alpha]pyrene (BP) and 3-methylcholanthrene (MCA) but had no effect on 9,10-dimethyl-1,2-anthracene (DMBA) initiation in a two-stage system of tumorigenesis in female Charles River CD-1 mice. The tumor-initiating ability of dibenz[alpha,h]-anthracene (DBA) was decreased by prior topical treatment with 10 mumoles of TCPO. The tumor latency period of BP and MCA was decreased by TCPO but had no effect on DMBA or DBA. Topical treatment with 10 mumoles of TCPO did not initiate tumors in a two-stage system in mouse skin nor did it cause any histopathologic changes in the skin. The "K-region" epoxides of BP, DMBA, and MCA were weak tumor initiators when compared to the parent compounds. TCPO only slightly increased or had no effect on the tumor-initiating activity of the above epoxides. Pretreatment with Croton oil 18 hours prior to initiation with BP-4,5-epoxide also slightly enhanced the tumorigenic response in mouse skin. DBA-5,6-epoxide, when tested as a complete carcinogen at high doses (1 mg daily/10 days), was found to be a weak carcinogen but with activity comparable to that of DBA. TCPO only slightly increased the in vitro epidermally mediated covalent binding of the above parent polycyclic hydrocarbons to DNA.
 ...
PMID:Effect of trichloropropene oxide on the ability of polyaromatic hydrocarbons and their "K-region" oxides to initiate skin tumors in mice and to bind to DNA in vitro. 40 93

A method was developed for continuously exposing tracheal epithelium to measured amounts of carcinogen. Beeswax was the vehicle for sustained release of carcinogen, and tracheas transplanted to s.c. sites were target tissues. In the experiment reported here, transplanted rat tracheas were exposed to a potent carcinogen, 7,12-di-methyl benz(a)anthracene (DMBA). The rate of release of DMBA from the beeswax carrier within the tracheal lumen approached first order when the initial concentration of carcinogen was high (3200 to 325 microng in a 24.45-mg pellet). With lower concentrations, where the carcinogen was dissolved in the beeswax, initial release was rapid, and most of the carcinogen was delivered within 4 weeks. At high DMBA dose levels, the entire tracheal epithelium was uniformly replaced by keratinizing squamous metaplasia after 1 week of exposure, and after 2 months, when from 280 to 910 microng DMBA had been delivered, all transplants had developed invasive squamous carcinomas. Sarcomas also developed in 19% of the transplants. At lower dose levels the epithelial reactions were more varied, and tumor development was more protracted. The lowest DMBA dose presently known to diduce carcinomas in this experimental model is 40 microng, which is in the dose range used for tumor initiation in skin carcinogenesis studies in mice.
 ...
PMID:Quantitative exposure of grafted rat tracheas to 7, 12-dimethylbenz(a)anthracene. 40 31

This study analyzed the effectiveness of a nonsteroidal antiestrogen, cis-(3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (U 23,469) previously shown to be potent in antagonizing estrogen-induced uterine growth, in preventing the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors and in eliciting the regression of established tumors; the study also attempts to elucidate the mechanisms of the tumor antagonism of U 23,469. Virgin female Sprague-Dawley rats that receive DMBA at 47 to 50 days of age and then receive U 23,469 (250 micrograms s.c. in 0.15 M NaCl daily) have a greatly reduced number of mammary tumors and a markedly decreased tumor area. Treatment with U 23,469 for increasing time periods (3, 6, or 12 weeks) beginning 2 weeks after DMBA results in a progressive delay in onset of tumor appearance. U 23,469 treatment beginning 1 week after DMBA or given prior to DMBA is even more effective. The time course of tumor regression (3 months after DMBA) by U 23,469 or ovariectomy is similar, with 50% regression in ca. 2 weeks, and both elicit regression of almost all tumors (greater than 90%). After ovariectomy, cytosol progesterone receptor levels are greatly diminished in tumors and uteri, while cytosol estrogen receptor (ER) levels are high; in both tissues little (ca. one-third) of ER is in the nucleus. During U 23,469 treatment, cytosol ER content is very low in regressing tumor and uterus and over 90% of ER is in the nucleus; cytosol progesterone receptor is slightly depressed in the uterus but is at the untreated level in mammary tumor. These receptor studies suggest that the effectiveness of this antiestrogen in antagonizing mammary tumor development and growth may reside in its ability markedly to perturb the distribution of ER, maintaining over 90% of ER in the nucleus with concomitant low levels of cytoplasmic ER, a situation that may render the mammary tissue insensitive to the animal's own endogenous estrogens.
 ...
PMID:Antagonism of development and growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by the antiestrogen U 23,469 and effects on estrogen and progesterone receptors. 40 32

The preneoplastic skin changes usually induced by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) to adult rat skin did not appear when animals were treated locally with depot im injections of high doses of retinyl palmitate (RP) prior to exposure to the carcinogen. The epidermal histology after RP-DMBA treatment was similar to that seen in areas exposed to RP alone. Keratinization was inhibited but there was no cellular atypia, evidence of cell injury, or mucous metaplasia. Other features were hyperplasia with acanthosis and thickened stratum granulosum, parakeratosis, intercellular edema, and loss of hair overlying the injection site. Ultrastructurally, the epidermal cells contained conspicuously fewer tonofibrils and increased dense chromatin, when compared to control cells. Skin changes observed following treatment of littermates with DMBA alone included the appearance of giant tumor cells, dyskeratotic cells, nuclear hyperchromatism, increased nucleocytoplasmic ratio, and pleomorphic nuclei and nucleoli. oss of desmosomes, increased tonofibrils, and defects in the basement membrane with epithelial projections into the dermis were also seen. These preneoplastic changes did not regress when application with DMBA was discontinued after 6 weeks; exposure to the carcinogen for longer than 6 weeks resulted in an exacerbation of the abnormal state. RP had profound effects on rat epidermis that interfered with the effects of a potent skin carcinogen. The mechanisms underlying the phenomenon have not been defined. The use of depot injections of the vitamin which avoids both systemic toxicity and the local irritation seen with topical exposure could serve as a model in which the anticarcinogenesis properties of retinoids could be explored.
 ...
PMID:Effects of depot injections of retinyl palmitate on 7,12-dimethylbenz[a]anthracene-induced preneoplastic changes in rat skin. 40 31

Preleukemic cells could be detected in the bone marrow cell population of SJL/J mice within several days after induction of leukemia by repeated feedings with a chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Bone marrow cells collected 7, 30 or 60 days following carcinogenic treatment, developed lymphoid tumors upon transplantation into syngeneic irradiated recipients. The incidence of these tumors varied between 40--45% when the bone marrow cells were collected and transferred 7--30 days after feeding with DMBA, and raised to an incidence of 80% when transferred 60 days after carcinogen administration (compared to 50% incidence in the DMBA-treated bone marrow donors). A survey of several cell surface components on the lymphoid tumor cells, obtained after transplantation of preleukemic cells, indicated that most of the tumor lines bore both the Thy-1.2 antigen (weak) and the Fc receptor, whereas the rest were positive only for the Fc receptor. None of these tumor cell lines would yield a significant amount of cell-bound immunoglobulin.
 ...
PMID:Cell surface components of carcinogen-induced lymphoid tumors in SJL/J mice. 40 24

The effects of benzoflavones on skin tumor initiation by polycyclic hydrocarbons and epidermal aryl hydrocarbon hydroxylase were investigated. 7,8-Benzoflavone (7,8-BF) was found to be a potent inhibitor of the inhibition of skin tumors by 3-methylcholanthrene (MC) as well as 7,12-dimethylbenz(a)anthracene (DMBA). 5,6-Benzoflavone(5,6-BF) inhibited tumor initiation by MC and DMBA, but to a lesser degree than 7,8-BF. Dose-response studies of the capacity of 7,8-BF to inhibit DMBA tumor initiation revealed that 7,8-BF was an effective inhibitor at 2.5 microgram and a maximum inhibition of 90% occurred at 100 microgram of 7,8-FB. The tumor initiating ability of 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHMe-12MeBA) was not inhibited by 7,8-BF. Epidermal aryl hydrocarbon(benzo(a)pyrene hydroxylase(AHH) was increased by 5,6-BF and either had no effect or was slightly inhibited by 7,8-BF when given either topically or i.p. Both flavones when added directly to the assay tubes inhibited the in vitro epidermal AHH activity from control and MC pretreated mice by greater than 75%. When added in vitro, 7,8-BF and 5,6-BF inhibited epidermally mediated covalent binding of radioactive DMBA and dibenz(a,h)anthracene to DNA by 50% or more. The inhibition of skin tumor initiation by 7,8-BF and 5,6-BF appears to be partially related to its ability to inhibit the formation of electrophilic intermediates.
 ...
PMID:The effects of benzoflavones on polycyclic hydrocarbon metabolism and skin tumor initiation. 40 10

Transplantable tumor lines were developed from 7,12-dimethylbenz[a]anthracene-induced mammary tumors in inbred WF rats. Although the primary tumors regressed following oophorectomy, the growth of late generations of the transplantable lines was not affected by castration or by treatment with estrogens, androgens, and progesterone. This result coincided with a change in the morphology of the tumors from well-differentiated to poorly differentiated anaplastic tumors. The transplantable mammary tumors were antigenic in vitro as evidenced by stimulation of syngeneic lymphocytes in mixed lymphocyte-tumor cell cultures. However, prior sensitization by excision of a first tumor graft failed to protect the animals against a second challenge with cells from the same tumor line.
 ...
PMID:Transplantable mammary tumors in Wistar/Furth rats: development, antigenicity, and effect of hormone manipulations. 40 5

Breast cancer was induced in female Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene. Once tumors had become established, they were treated with varying doses of the immunopotentiating drug, levamisole. Tumor growth was measured in the various dosage groups, and at 6 months after tumor induction the animals were sacrificed. Their immunological competence at this time was measured by the mitogen responses of splenic lymphocytes. Untreated animals with breast cancer were found to be immunosuppressed compared to normal animals. The drug levamisole resulted in immunopotentiation, but at high doses it was immunosuppressive. Tumor regression was observed at doses that resulted in immunopotentiation, but not at high doses. There was a significant correlation between immune competence and tumor regression. It is concluded that levamisole can cause regression of breast cancer in the rat but that this effect is critically dependent on the dose of the drug; these observations confirm previous studies carried out on human cells in vitro. It is recommended that high doses of the drug be avoided in human clinical trials and that the patients who receive this drug should have their immune responses carefully monitored.
 ...
PMID:Dose dependence of immunopotentiation and tumor regression induced by levamisole. 40 85

Five tumor-producing cell lines were established from explant cultures of adult C57BL mouse submandibular gland. Four lines were from cultures treated for 24 hr on Day 4 of culture with 7,12-dimethylbenz(a)anthracene. Three of these gave rise to adenocarcinomas after transplantation into syngeneic mice; the fourth produced tumors with carcinomatous and sarcomatous areas. The fifth cell line was derived from an untreated culture and gave rise to adenocarcinomas. A series of four well-defined morphological stages occurred in the cultures before tumor-producing cell lines were established. In Stage I (0 to 30 days) there was an outgrowth of epithelium; in Stage II (30 to 70 days) ductal differentiation occurred in some epithelium; in Stage III (70 to 100 days) small, slowly proliferating foci developed either from the ducts or from flat epithelial areas. In Stage IV (over 100 days) the proliferation rate in some of the foci increased, and the cells became more irregular. The cells could not be transferred easily until about 150 days, after which time they were tumor producing. Neoplastic transformation occurred between 158 and 240 days in the treated cultures and at 325 days in the untreated culture.
 ...
PMID:Stages in neoplastic transformation of adult epithelial cells by 7,12-dimethylbenz(a)anthracene in vitro. 40 88

Growth rates of 7,12-dimethylbenz(a)anthracene-induced mammary tumors and the specific 125I-labeled prolactin binding to membrane fractions prepared from livers and tumors were studied in rats made diabetic by streptozotocin injection. Growth was inhibited in a majority of tumors and prolactin binding was reduced in both tumors and livers from diabetic animals. Prolactin binding to individual tumors varied over a wide range in both intact and diabetic animals. Scatchard analysis of binding data revealed that the apparent affinity of prolactin binding to liver and tumor membranes was similar (Ka approximately 3.0 X 10(9) M-1) and was not affected by diabetes. We suggest that the reduction in prolactin binding to tumors may render these tissues less responsive to prolactin and thereby explain, at least in part, the observed inhibition of tumor growth in diabetic rats. However, some tumors in diabetic animals regressed despite relatively high levels of prolactin binding activity. Therefore, additional factors most certainly play important roles in the mechanism(s) by which the growth of 7,12-dimethylbenz(a)anthracene-induced tumors is impaired in the diabetic rat.
 ...
PMID:Prolactin binding to 7,12-dimethylbenz(a)anthracene-induced mammary tumors and liver in diabetic rats. 40 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>