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)

A maximum tolerated dose (15 mug/g) of the carcinogen 4-nitroquinoline 1-oxide (4NQO) induced neither fetal deaths nor malformations when given to pregnant ICR/Jcl mice at the sensitive stages (Days 9 to 11) for the induction of malformations, although these embryotoxicities were detected with urethan and X-ray. This may not be due to the lack of teratogenic actions of 4NQO, but to the difficulty this compound has in reaching the embryo, because direct injection of 4NQO into the amniotic cavity of the Day-11 embryo, so that exposure was more direct, induced a high incidence of malformations. Similarity of the mechanism of chemical carcinogen-initiated teratogenesis and carcinogenesis was also suggested by the following findings. Urethan-initiated teratogenesis was almost completely inhibited by posttreatment with caffeine during the period of 0 to 24 and 24 to 48 hr after urethan treatment, whereas it was not inhibited during the 48- to 72-hr post-urethan and the 6- to 30-hr pre-urethan period. The results are similar to those of 4NQO-initiated transformation in cultured mouse embryo cells and 4NQO- and urethan-initiated lung tumorigenesis in mice. Cells carrying preteratogenic or pretumorigenic damage produced by some chemical carcinogens may be extremely sensitive to caffeine treatment during and/or after the postcarcinogen DNA replication period, thus resulting in decrease of malformations and tumors. The process may be related to error-prone DNA repair, because caffeine is known to inhibit the postreplication repair in cultured mouse cells.
Cancer Res 1977 Apr
PMID:Similarity of the mechanism of chemical carcinogen-initiated teratogenesis and carcinogenesis in mice. 40 2

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.
J Natl Cancer Inst 1977 Apr
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

Butylated hydroxytoluene, butylated hydroxyanisole, and vitamins C and E are effective inhibitors of 7,12-dimethylbenz(a)anthracene tumor initiation in a two-stage system of tumorigenesis. These antioxidants did not significantly induce epidermal aryl hydrocarbon [benzo(a)pyrene]hydroxylase, nor did they have any effect when added directly to the in vitro aryl hydrocarbon [benzo(a)pyrene]hydroxylase assay. However, butylated hydroxytolene and butylated hydroxyanisole, when topically to mice, inhibited the in vitro, epidermally mediated, covalent binding of radioactive benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene to DNA. When butylated hydroxytolene and butylated hydroxyanisole were added in vitro, they did not inhibit the epidermally mediated covalent binding of the hydrocarbons to DNA. The inhibition of polycyclic hydrocarbon tumorigenesis by antioxidants may be related to the ability of antioxidants to prevent the in vivo activation of hydrocarbons to carcinogenic epoxides and/or other electrophilic intermediates or may be related to their ability to increase detoxification of the reactive intermediate that requires intact cells to be operational. In any event, the results suggest that the antioxidants have an indirect effect on the epidermal metabolizing system which leads to a decrease in covalent binding to DNA.
Cancer Res 1977 Jun
PMID:The effects of antioxidants on skin tumor initiation and aryl hydrocarbon hydroxylase. 40 33

Pituitary and serum levels of prolactin (PRL) and serum levels of progesterone (P) were determined by polyacrylamide gel electrophoresis and radioimmunoassays in BALB/c female mice, 15-17 or 44 weeks old, treated with chemical carcinogens. Neither 1.5 mg 3-methylcholanthrene (MCA) nor 1.5-6 mg 7,12-dimethylbenz(a)anthracene (DMBA) markedly altered pituitary or serum levels of PRL in the younger mice, though DMBA increased the total pituitary content of PRL by about 33% in the 44-week-old mice. However, this increase was not correlated with the incidence of mammary tumors in the group or individuals. MCA increased serum P levels by about 22% within 50 days of the last treatment. This increase was attributable to higher serum levels of P during the diestrous and proestrous phases of the cycle. Adrenalectomy reduced serum P levels by about 60%, wheras ovariectomy had no effect. Serum P levels in 44-week-old rats were not affected by DMBA. The results fail to support the notion that MCA and DMBA promote murine mammary tumorigenesis by increasing pituitary and serum prolactin concentrations.
J Natl Cancer Inst 1977 Jul
PMID:Mammary tumorigenesis in chemical carcinogen-treated mice. VII. Prolactin and progesterone levels in BALB/c mice. 40 13

During diethylnitrosamine (DEN) administration, a distinctive difference was observed between rats and guinea-pigs in the sequence of ultrastructural changes in the hepatic endoplasmic reticulum (ER). In DEN-induced hepatic tumour cells in the guinea-pig there was extensive proliferation of the rough ER, while the smooth ER was quite sparse; in the premalignant liver the opposite was noted. This is in contrast to the rat, in which administration of either DEN or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) brings about, in both premalignant and malignant hepatic tissue, proliferation of the smooth ER and sparsity of the rough ER. Yet, as in the rat, the number of ribosomes on the outer surface of the guinea-pig liver rough ER is greatly reduced and this is paralleled by a 49% decrease of the RNA/protein ratio as early as 4 weeks of nitrosamine administration. The decrease of RNA/protein ratio and ultrastructurally observed loss of ribosomes from the ER, following nitrosamine administration, correlate with a decrease of photometric response of microsomal suspensions to the sulphydryl probe, p-chloromercuribenzoate. While azo-dye-reductase activity is higher in untreated rats than in untreated guinea-pigs, feeding 3'-Me-DAB for 6 weeks brings about a 76% decrease in the rat, but no significant decrease in the guinea-pig, which is refractory to azo-dye carcinogenesis. Thus, the ability of the liver to inactivate the dye is greatly decreased in the rat, but not in the guinea-pig, as administration progresses toward the threshold dose for tumorigenesis. On the other hand, constitutive levels of nitrosamine dealkylase are identical in the 2 species and remain essentially unchanged following administration of DEN for 10 weeks. Inasmuch as nitrosamine dealkylation represents activating metabolism, this provides a rationale for the comparable susceptibility of the rat and guinea-pig to DEN carcinogenesis. Of the 2 enzymes in the 2 species, it is only azo-dye reductase in the guinea-pig which appears to be unregulated by glucose repression, since starvation brings about no change in this activity. Starvation-induced increase of azo-dye reductase in the rat is not influenced by administration of 3'-Me-DAB and only slightly by DEN. The starvation-induced increase of nitrosamine dealkylation is abolished, however, in both species by administration of DEN but only slightly decreased by 3'-Me-DAB.
Br J Cancer 1977 Dec
PMID:Ultrastructural and metabolic determinants of resistance to azo-dye susceptibility to nitrosamine carcinogenesis of the guinea-pig. 41 61

The effect of azaserine on the pancreatic tumorigenesis of 4-hydroxyaminoquinoline 1-oxide (4-HAQO) after partial pancreatectomy in rats was studied. Pancreatic acinar cell carcinomas were produced in 7 out of 10 rats (70%), which received 7 mg/kg body wt. 4-HAQO 3 days after partial pancreatectomy, followed by 10 weekly injections of 30 mg/kg body wt. azaserine. Partial pancreatectomy enhanced the carcinogenesis of 4-HAQO, which was further promoted by azaserine.
Cancer Lett 1978 Apr
PMID:Production of pancreatic acinar cell carcinoma by combined administration of 4-hydroxyaminoquinoline 1-oxide and azaserine in partial pancreatectomized rats. 41 3

The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mammary tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor appearance and greater tumor burden than did controls maintained on a diet containing 4.6% fat. These diet-associated changes were markedly inhibited by ovariectomy, indicating that the tumor growth was hormone responsive. We examined the possibility that the diet with increased fat content enhanced tumor growth through alterations in prolactin metabolism but could find no consistent elevation in serum prolactin and no increase in pituitary prolactin synthesis in vitro. Our data further showed that rats on an iodine-deficient form of the high-fat diet had no greater tumor growth than did animals receiving an iodine-supplemented form of the same diet. We conclude from these results that iodine deficiency does not promote mammary tumorigenesis. An incidental finding of great interest was that ovariectomy led to a highly significant depression of thyroid-stimulating hormone production in vitro. This suggests that estrogens may directly influence thyroid-stimulating hormone synthesis in vivo and thus contribute to the sex-related differences in thyroid physiology.
Cancer Res 1979 Mar
PMID:Effects of iodine deficiency and high-fat diet on N-nitrosomethylurea-induced mammary cancers in rats. 42 60

The effect of diethylstilbestrol propionate (DES; 1 mg/kg body wt. was studied in the female offspring of rats exposed subcutaneously on the 19th day of gestation. Examination of vaginal smears showed persistent estrus in adult rats treated prenatally with DES. Compensatory ovarian hypertrophy (COH) induced by hemicastration of these rats was not suppressed by estrogens. A per oral test for glucose-tolerance revealed decreased utilization of glucose in the offspring of DES-treated rats. Preliminary observations demonstrated that tumors developed in 14 of 18 (77.8%) progeny transplacentally expoed to DES and in 9 of 34 (26.5%) intact control rats. Tumors of the ovary and the endometrium were found only in the rats treated prenatally with DES; no tumors of the uterine cervix or vagina were observed in either experimental or control groups. It is suggested that a transplacental effect of DES in the female is impairment of the sex differentiation of the hypothalamus. The resulting hormonal and metabolic shifts might promote tumorigenesis.
Cancer Lett 1979 Feb
PMID:Transplacental effect of diethylstilbestrol in female rats. 43 10

Alcohol and tobacco appear to act synergistically in the pathogenesis of epithelial cancers of the oropharynx (excluding lip), larynx, and esophagus. For the subsites within the upper aerodigestive tract, over 10,000 deaths in United States men during 1978 may be attributed to tobacco and alcohol consumption. The cancer sites for which tobacco and alcohol are major determinants occur with greater frequency in men, blacks, lower socioeconomic groups, and with increasing urbanization and increasing age (35--70 years). Because primary hepatocellular carcinoma occurs more commonly in patients with cirrhosis, chronic alcohol abuse is an important risk mechanism for carcinoma of the liver parenchyma. Although experimental animal studies have failed to demonstrate whether ethanol can independently initiate tumorigenesis, various alternative or associated biochemical and immunological mechanisms of action have been proposed.
Cancer 1979 May
PMID:Alcohol as a co-factor in the etiology of cancer. 44 84

During studies of renal tumorigenesis induced by estrogen in Syrian hamsters, we have observed that about 15 to 20% of animals develop bladder lesions with an increased wet weight of tissue from 0.2 g to 0.4 to 1.7 g. Histological examination of the lesions showed a spectrum of changes from inflammatory reactions to squamous metaplasia and intense hyperplasia of the transitional epithelium. The concentration of progesterone-binding sites was increased in the bladders with lesions. No specific progesterone-binding sites could be detected in the cytosol of bladders from hamsters not treated with estrogen. The affinity constant for the progesterone-binding sites in cytosol from bladders with lesions was 10(9) M-1, the same as that reported for progesterone receptors in other target tissues for estrogen. The binding sites are specific for progesterone and are not competed for by 17 beta-estradiol, 5 alpha-dihydrotestosterone, or aldosterone.
Cancer Res 1979 Jul
PMID:Increased progesterone receptor concentrations in bladder lesions of estrogen-treated Syrian hamsters. 44 62


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