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

A partial, progressive loss of I-compounds (age-dependent, putative indigenous DNA modifications) has been observed recently during hepatocarcinogenesis induced in rats by 2,3,7,8-tetrachlorodibenzo-p-dioxin, choline-devoid diet or peroxisome proliferators. It was of interest, therefore, to investigate the status of I-compounds in hepatic neoplasms. I-compounds were measured by 32P-postlabeling in eight transplantable rat (Morris) hepatomas of different growth rates and in host liver. Most I-compounds seen in liver were not detected in any of the hepatomas, and those present exhibited low levels. Hepatomas displayed an overall level of one I-compound in 2 x 10(8) DNA nucleotides, which was 7-16 times lower than liver values. The extent of I-compound deficiency did not correlate with tumor growth rate. These results, taken together with previously documented pronounced tissue-, sex-, strain- and species-specificity of I-compound profiles, suggest that I-compounds are normal DNA modifications and that their deficiency may contribute to development and maintenance of neoplasia.
Carcinogenesis 1990 Jun
PMID:Lack of I-compounds in DNA from a spectrum of Morris hepatomas. 234 63

Influence of sex steroids on the growth of an azaserine-induced transplantable rat pancreatic carcinoma, DSL-2, was studied. This established transplantable tumor has been maintained in syngeneic rats. Inbred male Lewis rats were pretreated with castration and s.c. implantation of 1.0-mg 17 beta-estradiol (CAS: 50-28-2; estradiol) pellets at 7 weeks of age. Tumor cells were inoculated s.c. on the back of intact male, castrated male, or 17 beta-estradiol-treated castrated male rats. Additional male rats served as non-tumor-bearing controls. There was no difference in the body weight between tumor-bearing and non-tumor-bearing male rats. A distinct difference in the tumor growth was observed in variously conditioned recipients. In castrated male hosts, the serum testosterone levels and the epididymis weights were significantly decreased, and the tumor weights were significantly less as compared to intact control hosts. Additional pretreatment with 17 beta-estradiol caused a markedly slower growth of tumors and increases of the serum 17 beta-estradiol levels and the pituitary weights in castrated male recipients. The remarkable response of tumor growth to castration was also observed in a fast-growing tumor derived from DSL-2. Moreover, close positive relationships between tumor weights and the activities of both serum amylase and lipase were observed. Results showed that the pretreatment with castration alone or in combination with 17 beta-estradiol treatment was able to inhibit the growth of the transplantable tumor. In addition, tumor cells had an ability to produce amylase and lipase, and the amount of enzymic activity was related to the tumor volume. Thus, these data indicate that the transplantable rat pancreatic carcinoma retains physiological function. Our previous study has shown the modulation by sex steroids of azaserine-induced preneoplastic lesions of pancreas in rats. Therefore, androgens and estrogens may play key roles as promoters and inhibitors during the process of pancreatic carcinogenesis.
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PMID:Inhibition of a transplantable pancreatic carcinoma by castration and estradiol administration in rats. 247 69

Most previous studies on the inhibiting effect of caloric restriction during promotion of DMBA-induced mammary carcinogenesis have used low to moderate levels of dietary fat, i.e., about 4 to 14% by weight. The current study was designed to test whether a moderate degree of caloric restriction, 25%, would inhibit tumor growth in rats fed the equivalent of 20% dietary fat which approximates human consumption in affluent countries. Rats were fed diets ad libitum that contained 5, 15 or 20% corn oil. Groups of rats were pair-fed to the last 2 groups, but subjected to a 25% caloric restriction. These groups were fed 20 or 26.7% corn oil so that absolute fat intake in the paired groups was identical. Significant inhibition of tumor incidence, tumor weight, tumor burden, body fat deposition, and fasting serum insulin were observed in the 2 calorically restricted groups. We conclude that moderate caloric restriction is significantly more effective in inhibiting tumor growth than is the promoting effect of diets high in fat. Total body weight, body fat and serum insulin concentrations may be better correlates of risk of developing mammary tumors than is dietary fat.
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PMID:Inhibition of DMBA-induced mammary tumorigenesis by caloric restriction in rats fed high-fat diets. 249 75

We previously have shown that urine components capable of stimulating ornithine decarboxylase activity of urothelium can enhance rat urinary bladder carcinogenesis, and that alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, suppresses carcinogen-initiated rat urinary bladder carcinogenesis. The present investigation was conducted to determine whether DFMO's suppressive effect is stage specific during carcinogenesis and whether the suppressive effect lasts with its continued use. Following initiation with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine in drinking water for 6 wk, male Fischer 344 rats initially weighing 125 to 150 g were randomly divided into two groups, the first receiving 0.2% DFMO in drinking water ad libitum and the second receiving tap water only. Groups of animals were killed at regular intervals until the completion of the experiment at 75 wk. The effect of DFMO was evaluated by monitoring the incidence of tumors, the mean number of tumors per rat, the mean volume of individual tumors, and the mean total tumor volume per rat. The results showed that continuous treatment with DFMO significantly reduced tumor formation until 60 wk (P less than 0.017). The effect was only of borderline significance (0.017 less than P less than 0.035) at 75 wk. Discontinuation of DFMO treatment at 40 wk resulted in the loss of protective effect in all comparisons except for the borderline effect on the tumor number and total tumor volume per rat. DFMO had no significant effect on the incidence or development of preneoplastic early lesions. Mucosal polyamine (spermidine and spermine) levels were reduced and correlated well with the reduction in tumor growth, suggesting that the reduction in tumor growth rate by DFMO may be due to its ability to reduce polyamine levels in urothelium. There were no side effects attributable to DFMO treatment. DFMO may be a useful chemopreventive agent to retard the recurrence of human superficial bladder cancer.
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PMID:Inhibitory action of alpha-difluoromethylornithine on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat urinary bladder carcinogenesis. 250 87

Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.
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PMID:Cyclic AMP blocks expression of the c-sis gene in tumor cells. 254 92

The epidermal growth factor (EGF) and alpha-tumor growth factor are mitogenic proteins which bind to the EGF-receptor and may play a role in carcinogenesis or tumor progression. Our study investigated whether colorectal carcinomas and adenomas express altered levels of EGF-receptors or overproduce EGF-like activity by comparing histologically normal mucosa to carcinomas resected from the same patients. EGF-receptors were characterized by radioligand binding studies. Carcinomas contained unchanged or decreased levels of EGF-receptors in 13/16 and moderately increased levels in 3/16 patients as compared to normal mucosa. Adenomas obtained from 2 patients with familial polyposis coli and from a third patient with a coincident carcinoma had similar numbers of EGF-receptors as normal mucosa. EGF-like growth factors, in contrast, were significantly elevated in carcinoma extracts as compared to extracts from normal mucosa of the same patients. Adenomas did not contain elevated levels of EGF-like activity. We conclude that increased expression of EGF-receptors is infrequent in colonic adenocarcinomas. Increased production of EGF-like growth factors may frequently occur but seems to be associated with tumor progression rather than with premalignant lesions as represented by adenomas.
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PMID:Epidermal growth factor receptors and epidermal growth factor-like activity in colorectal mucosa, adenomas and carcinomas. 254 69

Our recognition that cancer evolves by clonal selection and that the basis for this selection is the growth advantage provided by the inappropriate expression or suppression of genes present in all normal cells allows us to anticipate that the pathways of this evolutionary process may be discovered. If a finite number of such pathways exist with some commonality between various tumors, there is the possibility to anticipate the mechanisms that cell clones might use for both carcinogenesis and tumor progression and to deal with evolving clones before their survival potential becomes overwhelming. As our biochemical understanding increases we may develop the capability to do the following: to identify individuals who have inherited or acquired defective cancer suppressor genes; to identify precursor lesions more exactly; to characterize the degree of progression of a newly diagnosed tumor (has the metastatic phenotype evolved?); to develop antibodies against cell membrane proteins necessary to tumor progression; to produce immune probes that carry cytotoxins or isotopes to specific cell populations; and to take advantage of cell signals to modify tumor growth. The potential for application of the New Biology to cancer medicine seems endless.
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PMID:The new biology of cancer: future clinical applications. 265 85

This paper provides an overview of our knowledge on the involvement in cancer of vitamins A, C and E and of calcium, selenium and zinc. This work is a background for studies on dietary magnesium's effects on cancer. Consumption of vitamin A and its dietary precursors has been associated with reduced cancer at several sites in human and animal studies. Carcinogenesis studies using several models of cancer have been conducted on the influence of vitamin A deficiency, vitamin A excess and supplementation of vitamin A analogues. Vitamins C and E are effective in the prevention of N-nitroso compound (nitrosamine) formation. Vitamin C is effective in aqueous and vitamin E is effective in non-aqueous media. Both of these vitamins also have inhibited carcinogenesis by preformed carcinogens at several sites, but enhancement has been observed at some sites when excess vitamin treatment was studied. The potential role of calcium in the prevention of colon cancer is being pursed. Few experimental studies have been conducted but data support an effect of calcium on colonic epithelial proliferation. Epidemiological and especially experimental results suggest an inhibition of cancer by dietary selenium. In animal studies, selenium supplementation has been particularly effective in inhibiting colon and mammary carcinogenesis, but enhanced carcinogenesis was observed in some studies on skin, liver and pancreas cancer. Data suggest that zinc deficiency may be a factor in esophageal cancer; however, studies on tumor growth have demonstrated retarded tumor growth in zinc-deficient animals.
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PMID:Effects of the intake of selected vitamins and minerals on cancer prevention. 266 27

N-Nitrosocimetidine (NCM) is a derivative of the drug cimetidine, a methylguanidine derivative used in the treatment of peptic ulcer, and is known to be inactive as a complete mouse skin carcinogen, even when given in repeated high doses for a long period. In the current experiment, NCM was tested for its ability to initiate skin tumors on Sencar mice. It was applied at doses of 1 or 0.3 mg, 5 times/week for 6 weeks, followed by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), 1 microgram, 2 times/week for 50 weeks. Controls received acetone. The higher NCM dose had significant effects on TPA-promotable tumors, resulting in shortened time to first tumor, increased incidence of all tumors (2-fold) and of malignant tumors (4-fold), and greater tumor growth rate (2-fold), compared with the acetone/TPA-treated mice. The mice given the lower NCM dose did not exhibit increased tumor incidence, but their tumors had a significantly higher growth rate (3-fold) than those of the TPA controls. NCM without TPA treatment caused no tumors. Thus, NCM is a definitive, though weak initiator of TPA-promotable tumors. Nine tumors from the NCM-treatment groups were analyzed for activated oncogenes by the NIH 3T3 cell transfection assay. Five were positive and four of these were found by selective oligonucleotide hybridization analysis to have an A to T transversion in the second position of codon 61 of the H-ras oncogene. One of two tumors from the acetone/TPA group also contained transforming DNA and demonstrated this mutation. None of the tumors had a G----A transition mutation at the second position of codon 12 of this oncogene. Tumor initiation by NCM may then be associated with the same oncogene mutation reported for mouse skin tumors initiated by other types of carcinogens, although occurrence of the mutated oncogene in TPA controls precludes a definitive conclusion.
Carcinogenesis 1989 Nov
PMID:N-nitrosocimetidine as an initiator of murine skin tumors with associated H-ras oncogene activation. 268 Jan 43

The role of cell membrane structures in the mechanism of anticarcinogenic and antiblastic action of retinoids was reviewed on the basis of the authors' results and data from literature. The retinoid action induced a delay and prevention of malignant neoplasms development, which is shown by various experimental models of carcinogenesis and tumour growth. The regulatory effect of retinoids on the membrane-bound enzymic processes was analyzed as very important in the clarification of the retinoid action mechanisms not only as antipromotor agents, but also as those influencing immediately the initiation stage of the tumour process. Improvement of the A-vitamin status of the organism is an important step in realization of the prophylactic programme of the tumor growth.
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PMID:[The role of membranes in the mechanisms of the anti-carcinogenic effect of retinoids]. 268 7


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