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

Despite the epidemiological evidence of a correlation between ethanol abuse and hepatocellular carcinoma, some of the results of experimental and clinical studies remain controversial. Apart from inducing cirrhosis, which may be viewed as a precancerous liver lesion, ethanol may act as a cocarcinogen. Most investigations on this topic have focused on two aspects: ethanol's capacity to induce the cytochrome P-450-dependent microsomal biotransformation system and its interference with at least one DNA repair mechanism. Ethanol exposure enhances the capacity of mixed function oxidases to activate many chemical carcinogens, such as dimethylnitrosamine (DMN). On the other hand, ethanol exposure fails to influence DMN-induced liver carcinogenesis. The capacity of alcohol to inhibit DMN-demethylase activity has not been clearly demonstrated in experiments carried out with human tissue. In conclusion, both the effects of ethanol and their underlying mechanisms as regards liver carcinogenesis are open to debate. The link between ethanol abuse and hepatocellular carcinoma appears to be mediated mainly by its capacity to induce cirrhosis.
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PMID:Hepatocellular carcinoma, alcohol, and cirrhosis: facts and hypotheses. 165 Jun 91

Although prior to its metabolic conversion alcohol has no mutagenic activity, an interaction of alcohol with tobacco in carcinogenesis of the head and neck region is well characterized. In a recent ecogenetic case control study of these cancers we documented an interaction between alcohol use and in vitro mutagen-induced chromosome damage in cancer risk. The present report evaluates the in vitro genotoxicity of five mutagens (including cigarette smoke condensate) tested in conjunction with 2% and 4% ethanol in human lymphoid cell lines. Ethanol alone did not exert a demonstrable clastogenic effect, as measured by the frequency of chromatid breaks per cell. However, the clastogenic potential of all mutagens increased when ethanol was added concurrently with the mutagens, and there was a dose-dependent potentiation of clastogenicity by ethanol, with a threshold dose between 0.5% and 1.0%. Preliminary experimental results strongly indicate that ethanol, at relatively high doses, inhibits DNA and chromosome repair systems. These data support the epidemiologic evidence of an interaction between alcohol and mutagens in carcinogenesis and suggest that alcohol may have co-carcinogenic properties.
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PMID:Ethyl alcohol as a cocarcinogen with special reference to the aerodigestive tract: a cytogenetic study. 171 84

Five groups of outbred white male rats were given N-nitrososarcosin ethyl ester (NSEE) i.g. for 4 or 6 months at a daily dose of 50 mg/kg of body wt. 5 days/week. Some groups of animals were given a 3% water solution of acetic acid or a 40% solution of ethanol i.g. for 8 months from the beginning of the experiment. The remaining groups of these rats received controlled local thermal burn injury of the esophageal mucosa 15 days before the beginning of the experiment. Acetic acid solution increased the multiplicity of benign and malignant tumors as well as carcinoma incidence in the esophagus. Ethanol in combination with NSEE did not influence carcinogenesis in the esophagus but increased the incidence of leukokeratosis and the multiplicity of forestomach papillomas. In rats treated with NSEE after thermal burn injury, a significant increase in the frequency and multiplicity of papillomas was found in the burn zone.
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PMID:The stimulating effect of acetic acid, alcohol and thermal burn injury on esophagus and forestomach carcinogenesis induced by N-nitrososarcosin ethyl ester in rats. 263 42

Preliminary dose finding studies showed that 22 mg/kg of N-nitrosomethylbenzylamine (NMBZA) delivered over 5 days did not induce esophageal lesions, but 18 mg/kg administered over a period of 2 or 3 weeks did induce these lesions. Based on these results, Sprague-Dawley rats were treated with 2.5 mg/kg NMBZA three times a week for 3 weeks to initiate esophageal carcinogenesis. The experimental animals were administered isocaloric ethanol diet either before and during NMBZA initiated carcinogenesis, or after initiation as a tumor promoter. The esophagi of rats that died or who were terminated at 18 months of age were examined for nodules and tumors. When ethanol was administered before and during initiation, the mean frequency of esophageal lesions was 8.04 +/- 3.04/rat with an average size of 1.44 +/- 0.27 mm versus 12.41 +/- 2.12/rat and 0.92 +/- 0.17 mm respectively for the controls. Only three out of 13 of the ethanol-fed rats had tumors (mainly squamous papillomas) versus 10 out of 26 of the control-fed animals. Ethanol consumption before and during initiation, therefore, decreased the incidence of esophageal nodules and tumors. With ethanol administered as a promoter, on the other hand, while incidence of the total lesions was not affected appreciably, the incidence of tumors was remarkably increased. With ethanol promotion the mean frequency of lesions was 8.75 +/- 1.07/rat with an average size of 1.02 +/- 0.09 mm versus 10.94 +/- 1.49/rat and 1.32 +/- 0.13 mm respectively for the controls. In this case, the ethanol-consuming rats had tumors in 14 out of 75 animals versus one small tumor in 32 of the controls. The results indicate that the occurrence of esophageal tumors is inhibited by simultaneous ethanol administration, but promoted when ethanol is administered post-initiation ostensibly by allowing extensive dysplastic proliferation of the carcinogen-induced lesions.
Carcinogenesis 1989 Feb
PMID:Effect of chronic dietary ethanol consumption on the initiation and promotion of chemically-induced esophageal carcinogenesis in experimental rats. 291 82

The effect of chronic ethanol ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body wt at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either separately or in combination with ethanol. Ethanol was provided in drinking water at a concentration of 10% (w/v). A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and received ethanol via their drinking water after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. Dietary fat was found to enhance pancreatic carcinogenesis in both rats and hamsters. In rats, ethanol slightly enhanced the multiplicity but not the incidence of malignant tumours, while in hamsters ethanol did not show any modulating effect on dietary fat-promoted carcinogenesis. It was concluded that dietary fat-promoted pancreatic carcinogenesis as observed in the animal models applied is not significantly modulated by chronic ethanol ingestion.
Carcinogenesis 1989 Mar
PMID:Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion. 292 93

The effect of dietary fat and ethanol and their interactions on the development of putative, preneoplastic foci in exocrine pancreas was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c., with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body wt at 6 and 7 weeks of age. The animals were fed a low fat (LF) control diet (5% corn oil) or a high fat (HF) diet (25% corn oil). Ethanol was provided in drinking water at a 15% (w/v) concentration. The animals were given the respective diets and ethanol after the treatment with carcinogen. At 4 months post-initiation, the pancreata were quantitatively examined for the number and size of preneoplastic foci. In rats, acidophilic as well as basophilic foci were subject to modulation by HF and ethanol. The results point to a specific promoting effect of unsaturated fat on the growth potential of azaserine-induced acidophilic acinar cell foci in rat pancreas. There was no evidence of an interaction between HF and ethanol as far as acidophilic foci are concerned. Evaluation of the number and size of the basophilic foci demonstrated an enhancing effect of ethanol on the modulation of pancreatic carcinogenesis by fat, pointing to a possible interaction between these two lifestyle factors. This suggestion was supported by the finding that six out of 20 rats in the HF with ethanol group exhibited a carcinoma in situ, whereas in the HF and in the ethanol group such an advanced lesion was found in one animal only. Unlike in rats, ethanol had no modulating effect on number and growth of putative, preneoplastic lesions in hamsters, either in combination with LF or in combination with HF. A HF diet, however, caused a significant increase in number as well as an increase in percentage of pancreatic tissue occupied by early lesions induced in hamster pancreas by BOP.
Carcinogenesis 1986 Sep
PMID:Modulation of putative preneoplastic foci in exocrine pancreas of rats and hamsters. I. Interaction of dietary fat and ethanol. 294 27

Ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide were tested for tumor-promoting activity in a two-stage stomach carcinogenesis experiment. Male outbred Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/liter) and a diet supplemented with 10% sodium chloride for 8 weeks. Thereafter, they were maintained on drinking water containing either 10% ethanol, 1% potassium metabisulfite, 0.5% formalin (formaldehyde) or 1% hydrogen peroxide for 32 weeks and then sacrificed for necropsy and histological examination. In the pylorus of the glandular stomach, potassium metabisulfite and formaldehyde significantly increased the incidence of adenocarcinoma after initiation with MNNG and sodium chloride. Hydrogen peroxide did not enhance the tumor yield, and ethanol showed a tendency to decrease neoplastic development. In the forestomach the incidence of squamous cell papilloma was significantly increased in the groups given hydrogen peroxide or formaldehyde, irrespective of prior initiation. Duodenal adenocarcinoma was induced by the initiation alone (10%) and the incidence was not affected by the subsequent treatments. The results indicate that potassium metabisulfite and formaldehyde both exert tumor-promoting activity in the rat glandular stomach.
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PMID:Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine. 308 23

There is an epidemiologic association between beer consumption and rectal cancer. Beer and ethanol were tested in the rat-dimethylhydrazine (DMH) experimental carcinogenesis model in order to verify this observation. Ethanol was found not to affect the number of colonic tumors induced by DMH (86 vs. 77 controls, P = 0.764). In rats fed beer and treated with DMH, there was a decrease in gastrointestinal tumor induction (P = 0.043). This instance then becomes one of many in which conclusions drawn from epidemiologic studies have been contradicted when subjected to analysis in an experimental colon carcinogenesis model.
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PMID:Neither dietary ethanol nor beer augments experimental colon carcinogenesis in rats. 400 41

Ethanol (E) was given to outbred Syrian golden hamsters in drinking water at a 5% (wt/vol) concentration for life beginning either before or after a single dose of N-nitrosobis(2-oxopropyl)amine (BOP). No effects on tumor induction were seen in the pancreas or in other BOP target tissues (e.g., the common duct and gallbladder), whether E was given immediately after or 4 weeks before and immediately after BOP. These results sharply conflicted with our previous findings in which a higher concentration of E (25% wt/vol) inhibited BOP-induced pancreatic lesions, and they indicated a dose-related action of E on pancreatic carcinogenesis. Development of a few acinar cell foci in hamsters treated with BOP and E, but not in those treated with E alone or BOP alone, indicated that E in this concentration alters pancreatic functions without modifying carcinogenesis.
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PMID:Modification of pancreatic carcinogenesis in the hamster model. XII. Dose-related effect of ethanol. 631 10

Alcohol consumption is associated with an increase in human cancer, notably of the oesophagus. We have found that ethanol will alter profoundly the distribution of two carcinogenic nitrosamines in the rat. Small oral doses of dimethylnitrosamine (NDMA) are absorbed from the portal blood as it passes through the liver, and do not reach the extrahepatic organs. Ethanol, equivalent to a man drinking 1 pint (0.5 l) of beer, prevents this first pass clearance in the rat and exposes sensitive extrahepatic organs to this carcinogen. As a consequence the alkylation of kidney DNA by 35 micrograms NDMA/kg body weight was increased 4.6-fold by concurrent administration of 240 mg ethanol/kg, and smaller doses of [14C]-NDMA produced detectable alkylation of kidney DNA only if the rats were given ethanol. Measurement of metabolism of NDMA by liver slices confirmed that this action of ethanol is the result of inhibition by ethanol of NDMA metabolism in liver (Ki = 0.5 mM). Comparison of urinary excretion in man and rat suggests that ethanol also inhibits first pass clearance of NDMA in man. There was no complete first pass clearance of diethylnitrosamine (NDEA), but while ethylation of kidney DNA was decreased by ethanol, that of oesophageal DNA was increased between 1.8- and 4.6-fold. Measurement of the metabolism of NDEA to CO2 by liver slices, kidney slices, and oesophageal epithelium suggest that the changes in alkylation of kidney and oesophageal DNA are the result of selective inhibition of NDEA metabolism in liver and kidney. The ethylation of oesophageal DNA was greater relative to liver after a small dose than after a large dose possibly because of the low Km of the oesophageal metabolic activating system relative to that in liver and kidney. These results explain experiments showing that concurrent administration of ethanol increases the carcinogenicity and alters the organs affected by these nitrosamines. It is tentatively proposed that the effect of ethanol on human cancer incidence is mediated through similar influences on the metabolism and disposition of the nitrosamines to which man is exposed.
Carcinogenesis 1984 Oct
PMID:Ethanol and dimethylnitrosamine and diethylnitrosamine metabolism and disposition in the rat. Possible relevance to the influence of ethanol on human cancer incidence. 643 99


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