Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to clarify the role of gut microflora in tumorigenesis by a comparison of tumor production between male germ-free and conventional Wistar rats given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 100 microgram/ml in drinking water. Ninety-one % of conventional MNNG-treated rats that died or were killed by Day 314 of the experiment developed tumors in the gastrointestinal tract, whereas only 17% of germ-free treated rats developed such tumors. In addition, large tumors, some 5 cm or more in diameter, were frequently observed in the conventional rats, whereas only small tumors 0.4 to 1.2 cm in diameter were present in the germ-free rats. Furthermore, multiple tumors including double tumors were often found in the conventional rats, while such tumors never appeared in the germ-free rats. The results suggest that gut microflora might exert a promoting influence on tumorigenesis by MNNG in the gastrointestinal tract. The promoting influence of the microflora in conventional rats might not be of a simple nature, since the influence of a variety of factors modified by the micorflora on tumorigenesis by MNNG p.o. is unavoidable.
Cancer Res 1979 Jul
PMID:Gastrointestinal carcinogenesis in germ-free rats given N-methyl-N'-nitro-N-nitrosoguanidine in drinking water. 44 76

The abilities of 3-methylcholanthrene (3-MC) and 3,11-dimethylcholanthrene (3,11-DMC) to initiate skin tumors in Sencar mice were determined by using a 2-stage system of tumorigenesis. 3,11-DMC was found to have very weak skin tumor initiating activity when compared to the potent activity of 3-MC. The only difference between 3-MC and 3,11-DMC is the substitution of a methyl group in position 11 which is part of the 'K-region' or the 'peri' position. From these results, we suggest that an unhindered peri position adjacent to an angular benzene ring is necessary for carcinogenic activity of 3-MC.
Cancer Lett 1979 Jul
PMID:Comparison of the skin tumor initiating activity of 3-methylcholanthrene and 3,11-dimethylcholanthrene in mice. 47 15

Several azido fluorenes, photosensitive analogs of the established carcinogen 2-acetylaminofluorene, have been synthesized to serve as probes in chemical carcinogenesis and mutagenesis studies. Unlike 2-acetylaminofluorene, these compounds do not require metabolic activation. However, alkylation to critical targets is achieved through the generation of nitrenes by photolysis at 360 nm in situ. We have found that the bifunctional azidofluorenes 2,5-diazidofluorene and 2,7-diazidofluorene were more toxic to and more transforming of the mouse embryo C3H 10T1/2 clone 8 cells when photolyzed in situ than were the monofunctional azides 2-azidofluorene and 7-bromo-2-azidofluorene. When the drugs were photolyzed in phosphate-buffered saline (pH 7.4) and then added to the cells these preirradiated derivatives were not transforming but were slightly toxic. However, there is not relationship between the number of photosensitive azido groups and the cytotoxicities of the preirradiated derivatives as measured by the plating efficiency method. The transformation experiments were performed under conditions in which photolysis was carried out for as little as 15 sec. This is significant because the major events that lead to oncogenesis apparently can occur within this narrow time channel, thereby making the drugs excellent probes in studies in chemical carcinogenesis. Although near ultraviolet light alone may transform the cells (8 to 16 min of irradiation), under the conditions studied ultraviolet light was neither toxic nor transforming.
Cancer Res 1979 Oct
PMID:Establishment of photoaffinity label derivatives of fluorene as probes in studies of chemical carcinogenesis in mammalian cell culture. 47 26

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an extraordinarily potent toxin, has recently been found to be a potent carcinogen producing mucosal, lung, and liver tumors in female rats. In light of this carcinogenicity, we reexamined the in vivo covalent binding of [3H]TCDD to rat liver macromolecules. Immature Sprague-Dawley rats, receiving [3H]TCDD (0.87 mCi/kg; specific activity, 39 Ci/mmol) concentrated 18 to 64% of the total administered dose in their livers, but virtually all of this radioactivity (greater than 99.9%) was extractable. The maximum unextractable radioactivity was: protein, 60 pmol TCDD per mol of amino acid residue; rRNA, 12 pmol TCDD per mol of nucleotide residue; and DNA, 6 pmol TCDD per mol of nucleotide residue. If one assumes that this small residual amount of radioactivity represents covalent binding, this binding is 4 to 6 orders of magnitude lower than that of most chemical carcinogens, and the binding to DNA is equivalent to one molecule of TCDD per DNA, equivalent to 35 cells. The results suggest it is unlikely that TCDD-induced oncogenesis is through a mechanism of covalent binding to DNA and somatic mutation.
Cancer Res 1979 Sep
PMID:An estimate of the maximum in vivo covalent binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to rat liver protein, ribosomal RNA, and DNA. 47 64

The age-dependent onset of spontaneous testicular interstitial cell tumors was examined in F344 male rats. Light microscopy of testes established that nodular interstitial cell hyperplasia was evident in 3 of 5 12-month-old rats and in 5 of 5 rats at 15, 18, 21, and 24 months of age. Involution of the seminiferous epithelium was evident in all testes exhibiting extensive interstitial cell proliferation. Striking increments in serum prolactin and estradiol levels were noted with advancing age, whereas serum levels of follicle-stimulating hormone were unequivocally lower at 21 and 24 months than at 6 months of age. No measurable changes were detected in serum testosterone concentrations between 6 and 18 months of age, but marked increments in this androgen, without any measurable change in circulating luteinizing hormone titers, were apparent in 21- and 24-month-old rats. These findings point to a dynamic relationship between testicular interstitial cell tumorigenesis and age-related changes in the synthesis and/or secretion of gonadal and adenohypophyseal hormones.
J Natl Cancer Inst 1979 Oct
PMID:Development of Leydig cell tumors and onset of changes in the reproductive and endocrine systems of aging F344 rats. 48 Mar 89

Five to ten daily injections of 5--20 micrograms 17 beta-estradiol, 20--100 micrograms testosterone and its propionate, and 100 micrograms 5 alpha-dihydrotestosterone starting within 24 hours after bith caused estrogen-independent persistent proliferation and cornification of the vaginal epithelium in female mice of the C57BL/Tw, C57BL/Ms, A/Ms, and A/CrgI strains. The permanently changed vaginas frequently resulted in tumorigenesis. In C57BL/Tw mice, some undifferentiated cells, which survive only for a few postnatal days in normal animals, appeared to transform into large cells and formed nodules after neonatal administration of 17 beta-estradiol. The primary normal epithelium was replaced by a sheet of fused nodules that showed persistent proliferation and cornification independent of estrogen. Occurrence of the estrogen-independent vaginal epithelium in C57BL mice receiving neonatal injections of 20 micrograms estradiol for 5 days was prevented by injections of 200 IU VA when given simultaneously with the estradiol. Light cells were found by electron microscopy in the epithelium of estradiol-plus VA-treated mice. How these cells may have prevented the occurrence of the permanently changed vaginal epithelium is discussed.
Natl Cancer Inst Monogr 1979 May
PMID:Development of permanently proliferated and cornified vaginal epithelium in mice treated neonatally with steroid hormones and the implication in tumorigenesis. 48 81

Syrian golden hamsters were given PuO2/ZrO2 particles via inhalation and/or Pu-laden ZrO2 ceramic 10-micron diameter microspheres lodged in the capillary bed of the lung. The mean initial lung burdens ranged from 8 nCi to 143 nCi for the six experimental groups of animals. Significant numbers of primary lung tumors (5-50% per group) were induced in those animals that received inhalation exposures. Additional alpha radiation administered via Pu-laden intravenous microspheres had little or no effect on tumorigenesis or the production of non-neoplastic, degenerative changes in the respiratory tract.
Int J Cancer 1979 Nov 15
PMID:Lung tumors from PuO2-ZrO2 aerosol particles in Syrian hamsters. 52 76

We compared the effects of chronic treatment with 2-Br-alpha-ergocryptine (CB-154) and of ovariectomy on the genesis of mammary hyperplastic nodules (HN) and mammary tumors in the C3H/He mouse. CB-154 is an established potent suppressor of pituitary prolactin. Eighty-five 21- to 25-day-old female mice were divided into three groups. Group I received daily sc injections of 0.1 mg CB-154. Group II was ovariectomized and group III served as controls. Mice were examined weekly for mammary tumors. Fifteen months from onset of treatment all surviving mice were killed. The mean number of HN per inguinal mammary gland, total number of mammary tumors, and number (percent) of mice with mammary tumors in each group were, respectively: controls--4.6 +/- 1.1, 41, 24/29 (83%); ovariectomized--1.2 +/- 0.6, 20, 14/28 (50%); and CB-154-treated--0.2 +/- 0.1, 16, 13/28 (46%). A significant (P less than 0.001) and equally comparable inhibition of mammary tumor incidence was observed in the ovariectomized and CB-154-treated mice. Thus early ovariectomy and CB-154 treatment (specific inhibition of prolactin secretion) appeared equally effective in the prophylaxis of mammary tumorigenesis in the C3H/He female mouse.
J Natl Cancer Inst 1977 Apr
PMID:Suppression of mammary tumorigenesis in C3H/He mice by ovariectomy or treatment with 2-bromo-alpha-ergocryptine: a comparison. 57 23

Topical administration of diethyl maleate (DEM) and L-methionine sulfoximine (MS) reduced the L-glutathione (GSH) levels in kidneys, livers, and skin of inbred BALB/c mice. Topical administration of DEM to BALB/c mice also increased the latency period before development of skin tumors that were induced by 3-methylcholanthrene painting. Similar treatment with MS also increased the latency period, though the delay was not as striking as that observed after DEM administration. Furthermore, DEM, which was believed to be specific in its action in reducing tissue GSH, was also capable of inhibiting aryl hydrocarbon hydroxylase (AHH) both in vitro and in vivo. Cyclohexene sulfide, another "specific" inhibitor of GSH transferase, inhibited AHH activity as well. Accordingly, the blockade of AHH by DEM may have been partly responsible for the increased latency time in the skin tumorigenesis experiments.
J Natl Cancer Inst 1978 Feb
PMID:Effects of diethyl maleate on aryl hydrocarbon hydroxylase and on 3-methyl-cholanthrene-induced skin tumorigenesis in rats and mice. 62 51

The skin tumor-initiating activities of the 12 isomeric phenols of benzo(a)pyrene (BP) were determined in mice by use of a two-stage system of tumorigenesis. 11-Hydroxybenzo(a)pyrene was moderately active, whereas 2-hydroxybenzo(a)pyrene and BP were strong tumor initiators when applied topically to CD-1 mice and followed by twice-weekly applications of the promoter 12-O-tetradecanoylphorbol-13-acetate. 1-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, and 12-hydroxybenzo(a)pyrene had less than 5% of the tumor-initiating activity of BP when the data were expressed as papillomas per mouse. After 30 weeks of promotion, the number of papillomas per mouse was 8.4, 8.5, and 2.8, respectively, for the animals treated with BP, 2-hydroxybenzo(a)pyrene, and 11-hydroxybenzo(a)pyrene. A 5-week latency period before the appearance of the first tumor was observed after the application of either 2-hydroxybenzo(a)pyrene or BP, whereas a slightly longer latency period of 7 weeks was observed following application of 11-hydroxybenzo(a)pyrene. The time required for 50% of the animals to develop tumors was 13 weeks for animals treated with BP and 15 weeks for animals treated with 2- or 11-hydroxybenzo(a)pyrene.
Cancer Res 1978 Mar
PMID:Skin tumor-initiating activities of the twelve isomeric phenols of benzo(a)pyrene. 62 71


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