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Diet, Nutrition, and Cancer (1982) / Chapter Skim
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12 Naturally Occurring Carcinogens
Pages 234-276

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From page 234...
... For example, very low levels of exposure to chemicals with relatively weak carcinogenic activity in laboratory animals may pose little risk to human populations. On the other hand, the presence of aflatoxin B1 in foods is a matter of great concern, since aflatoxin B1 is a potent carcinogen for a number of species and epidemiological data suggest that this carcinogen may play a role in the development of cancer in humans living in some parts of Africa and in the Far East (Peers et al., 1976; van Rensburg et al., 1974~.
From page 235...
... The scattered data pertaining to worldwide occurrence of aflatoxins in food were compiled for a conference on mycotoxins, which was sponsored by the Food and Agriculture Organization, the United Nations Environment Program, and the World Health Organization (1977~. More recently, Stoloff (in press)
From page 236...
... They further noted that there were no areas where high levels of aflatoxin ingestion have been associated with low rates of liver cancer. Although the studies described above suggest that aflatoxin causes primary hepatocellular carcinoma (PHC)
From page 237...
... The liver cells of these individuals are believed to regenerate more rapidly, thereby increasing the likelihood that a biochemical lesion that initiates neoplasia will become fixed in the genes of the subsequent cell population. The worldwide occurrence of hepatitis B viral infection is similar to that of primary hepatocellular carcinoma.
From page 238...
... Although most of these mycotoxins are mutagenic in bacterial systems and other short-term tests and/or are carcinogenic in laboratory animals, there are no epidemiological studies pertaining to their role in neoplasia in humans. Summary and Conclusions: M l~to~ns amd Othec ~ycocu~i``s A consistent body of evidence, all based on correlational data, associates the contamination of foods by aflatoxin with a high incidence of liver cancer in parts of Africa and Asia, but there is no epidemiological evidence that aflatoxin contamination of foodstuffs is related to 12-5
From page 240...
... N'-Acetyl-4-(hydroxymethyl~phenylhydrazine as a 0.0625% solution in drinking water administered continuously to Swiss mice from 6 weeks of age to the end of their lives induced lung and blood vessel tumors (Toth et al., 1978~. 4-(Hydroxymethyl~benzenediazonium tetrafluoroborate administered to Swiss mice in 26 weekly subcutaneous injections at 50 ~g/g bw resulted in an increased incidence of tumors of the subcutis and skin (Toth _ al., 1981~.
From page 241...
... Drinking water solutions of 0.001% hydrazine, 0.01% methylhydrazine, and 0.001% methylhydrazine sulfate were administered continuously to 5and 6-week-old randomly bred Swiss mice for their lifetimes. Hydrazine 12-8
From page 242...
... . A 0.01% solution of methylhydrazine was administered daily in the drinking water of 6-week-old randomly bred Syrian golden hamsters for the remainder of their lifetimes.
From page 243...
... Safrole has induced lowto-moderate incidences of hepatic tumors in adult rats fed at levels of 0.5% or more of the diet for as long as 2 years (International Agency for Research on Cancer, 1976~. Both safrole and estragole induced hepatic tumors and subcutaneous angiosarcomas within 18 months after they were fed to adult female CD-1 mice at levels of 0.25%-0.5% for approximately 1 year (Miller _ al., 1979~.
From page 244...
... The carcinogenicity of bracken fern was first suspected by Pamukcu in 1960, who found polyps in the urinary bladder mucosa of cattle fed large amounts of bracken fern for long periods (Pamukcu and Bryan, 1979~. Since that time, ingestion of high levels of bracken fern (25% to 40% of the diet)
From page 245...
... Carcinomas of the intestine, urinary bladder, and kidney pelvis were observed in rats fed high levels of fresh or powdered milk from cows that had consumed 1 g of bracken fern per kilogram of body weight daily for approximately 2 years, but not in rats fed milk from control cows (Pamukcu et al., 1978~. Estrogenic Compounds The plant estrogens include estrone (from palm kernels)
From page 246...
... Coffee Epidemiological Evidence: Carcinogenicity: Coffee drinking has been associated with elevated risk for bladder cancer in several casecontrol studies (Bross and Tidings, 1973; Cole, 1971; Fraumeni et al., 1971; Howe _ al., 1980; Miller et al., 1978; Simon et al., 1975;_ _ _ _ Wynder and Goldsmith, 1977~. However, with only two possible exceptions in males (Bross and Tidings, 1973; Wynder and Goldsmith, 1977)
From page 247...
... reported that readily oxidized phenolic compounds -- which are constituents of coffee -- catalyze nitrosamine formation from nitrite and secondary amines at gastric pH. For example, these experiments showed that 4-methylcatechol and the phenolic component of chlorogenic acid (approximately 13% of the dry weight of the soluble constituents of coffee)
From page 248...
... The methylating species formed from MAM and Cycasin appears to be similar or identical to that formed during the metabolic activation of the synthetic carcinogen nitrosodimethylamine, which has carcinogenic properties similar to those of Cycasin (Magee et al., 1976~. Experimental Evidence: Mutagenicity.
From page 249...
... Experimental Evidence: Carcinogenicity. The investigations of l Korpassy showed that subcutaneous administration of tannic acid in doses of 150 to 200 mg/kg bw produced skin necrosis, ulcers, and hepatic tumors in rats (Korpassy, 1959, 1961; Korpassy and Mosonyi, 1950, 1951~.
From page 250...
... (International Agency for Research on Cancer, 1976~. Experimental Evidence: Carcinogenicity Sarcomas resulted within 2 years in rats that had received repeated subcutaneous injections of parasorbic acid in total doses of either 13 or 128 mg per animal (International Agency for Research on Cancer, 1976~.
From page 251...
... However, lung adenomas were induced in mice with a single dose of O.O1 mg/g bw (Nomura, 1975~. The significance of naturally occurring ethyl carbamate in foods in the development of human cancer is unknown, but the levels are very low in comparison to those used to induce tumors in laboratory animals (i.e., the consumption of 5 ~g/day by a 70-kg person would provide an annual intake of approximately 0.05 ~g/g bw)
From page 252...
... Other dietary sources include nitrate-rich drinking water and fruit juices. More than one-third of the average daily intake of nitrite is contributed by the ingestion of cured meats, approximately one-third by baked goods and cereals, and less than one-fifth by vegetables.
From page 253...
... Epidemiological Evidence Studies conducted in Colombia, Chile, Japan, Iran, China, England, and the United States (Hawaii) have indicated that there is an association between increased incidence of cancers of the stomach and the esophagus and exposures to high levels of nitrate or nitrite in the diet or drinking water.
From page 254...
... by gastric cancer patients and by controls. Bladder cancer has been correlated with nitrate in the water supply or with urinary tract infections in some epidemiological studies (Howe et al., 1980; Wynder et al., 1963~.
From page 255...
... Approximately 300 different N-nitroso compounds have been tested, and a majority of them have been shown to induce cancer in various tissues of one or more species of laboratory animals when administered by any of several routes (Preussmann and Steward, personal communication, 1981~. In addition to both nitrosodimethylamine and nitrosodiethylamine, a number of other N-nitroso compounds detected in the environment are carcinogenic in animals (see, for example, Druckrey et al., 1967; Preussmann et al., 1981~.
From page 256...
... However, the findings from several epidemiological studies of certain geographical/nationality groups are consistent with the hypothesis that exposure of humans to high levels of nitrate and/or nitrite may be associated with an increased incidence of cancers of the stomach and esophagus. In these studies, the level, duration, and time of exposure were not studied in relation to cancer incidence, and exposure to other known or suspected carcinogens was not excluded.
From page 257...
... However, no evidence has been presented for the carcinogenicity of pyrrolizidine alkaloids and cycasin in humans, although there is unsubstantiated speculation that they may be involved in the development of neoplasia in humans. Other plant constituents, such as methylxanthines, thiourea, tannins, coumarin, parasorbic acid, safrole, estragole, and eugenol, and plant estrogens, such as zearalenone, are carcinogenic in laboratory animals and/or mutagenic in bacterial or mammalian cell systems.
From page 258...
... There is some inconclusive epidemiological evidence that nitrate, nitrite, and N-nitroso compounds play a role in the development of gastric and esophageal cancer. Many of the naturally occurring substances discussed in this chapter have been found to be carcinogenic in laboratory animals and/ or mutagenic in bacterial and other systems, thereby posing a potential risk of cancer in humans.
From page 259...
... 1973. Occurrence of a primary liver carcinoma in a rhesus monkey fed aflatoxin B1.
From page 260...
... 1973. Another look at coffee drinking and cancer of the urinary bladder.
From page 261...
... 1979. Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis.
From page 262...
... Nature 265:753-755. Food and Agriculture Organization, United Nations Environment Program, and World Health Organization.
From page 263...
... 19 77. Demonstration of the presence of nitrosamines in human urine: Preliminary observations on a possible etiology for bladder cancer in association with chronic urinary tract infection.
From page 264...
... Volume 10, Some Naturally Occurring Substances. International Agency for Research on Cancer, Lyon, France.
From page 265...
... 1951. The carcinogenic action of tannic acid effect of casein on the development of liver tumours.
From page 266...
... 1981. A multifactorial model for pancreatic cancer in man: Epidemiological evidence.
From page 267...
... 1979. Naturally Occurring Carcinogens-Mutagens and Modulators of Carcinogenesis.
From page 268...
... Part 1 of a 2-Part Study by the Committee on Nitrite and Alternative Curing Agents in Food. National Academy Press, Washington, D.C.
From page 269...
... 1978. Carcinogenic and mutagenic activities of milk from cows fed bracken fern (Pteridium aquilinum)
From page 270...
... 1981. Transformation of Syrian hamster embryo cells by diverse chemicals and correlation with their reported carcinogenic and mutagenic activities.
From page 271...
... 1979. In vitro assays for recombinogenic activity of chemical carcinogens and related compounds with Saccharomyces cerevisiae D3.
From page 272...
... 1975. Coffee drinking and cancer of the lower urinary tract.
From page 273...
... 1979. Carcinogenic effects in the Syrian golden hamster of N-methyl-N-fonmylhydrazine of the false morel mushroom GYromitra esculenta.
From page 274...
... 1981. Cancer induction in mice with acetaldehyde methylformylhydrazone of the false morel mushroom.
From page 275...
... 1974. Primary liver cancer rate and aflatoxin intake in a high cancer area.
From page 276...
... 1972. Letter to the Editor: Coffee and bladder cancer.


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