Liver cancer incidence

It seems that large numbers of chemicals, in equally large numbers of test systems, from mammals to insects, vertebrates to invertebrates, microorganisms to plants, exhibit hormetic dose-response relationships. The relationship is not the same as that described earlier for nutrients, in two ways. First, in the case of hormesis the biological response - the toxicity endpoint - is the same in the protective region and in the region of toxicity (i.e., liver cancer incidence is reduced relative to control incidence over a range of low doses, and then as the NOAEL is exceeded, liver cancer incidence increases above that of controls). This is true hormesis. 

Tu, and Z. H. Liu. Antimutagenic ef- SI113 feet of eight natural foods on moldy foods in a high liver cancer incidence area. Mutat Res 1992 279(1) 35-40. 

Thus, the type of exposure, continuous for lifetime versus intermittent or short-term exposure, appears to strongly influence the low dose-response curve. The cumulative exposure of 2 mmol/kg yielded a 92% liver cancer incidence... 

Novotna E, David A, Malek B. 1979. [An epidemiological study of hepatic tumor incidence in subjects working with trichloroethylene. I. Negative result of retrospective investigations in subjects with primary liver cancer. ] Prac Lek 31 121-123. (Czech)... 

Paddle GM. 1983. Incidence of liver cancer and trichloroethylene manufacture Joint study by industry and a cancer registry. Br Med J 286 846. 

In Greece, a case-control study was conducted to investigate the incidence of liver cancer by estimating the consumption of six types of flavonoids with a semiquantitative questionnaire on the frequency of foods. The intake of flavones was inversely associated with hepatocellular carcinoma, irrespective of its etiology (viral or nonviral). With respect to cholangiocarcinoma, an inverse association with the consumption of flavan-3-ols, anthocyanidins, and total flavonoids studied was found. However, this last result should be viewed with caution because of the small sample size, due to the fact that this is a rare type of cancer (Lagiou and others 2008). 

Two Russian studies suggested an increased incidence of lung and skin cancers in chloroprene-exposed workers compared with a variety of control groups." A more recent retrospective cohort mortality study among Russian shoe factory workers found an increase in the mortality from liver cancer that was associated with chloroprene exposure." A US study of cancer mortality among two cohorts of... 

Chronic oral exposure to heptachlor increased the incidence of liver carcinomas in three species of mice and one species of rats. A study of two cohorts of workers exposed to chlordane and heptachlor at two different production facilities failed to demonstrate any overall excess of cancer. There was one death from liver cancer with 0.59 expected. There was a slight excess of lung cancer (12 observed. 

Following intravenous injection of Thorotrast in humans and animals, various malignancies were found, primarily liver cancers (latency period of 25-30 years), leukemia (latency period of 20 years), and bone cancers (latency period of about 26 years). Short-lived daughter products of thorium also resulted in the induction of bone sarcoma because of their short radioactive half-lives. Intravenous injection of thorium-228 resulted in dose-dependent induction of bone sarcoma in dogs (Lloyd et al. 1985 Mays et al. 1987 Stover 1981 Wrenn et al. 1986). At the highest administered level, the animals died from systemic radiological effects (e.g., radiation induced blood dyscrasia and nephritis) before the bone sarcoma could develop (Stover 1981 Taylor et al. 1966). A relationship was found between the amount of thorium-227 (half-life of 18.7 days) injected intraperitoneally and the incidence of bone sarcoma in mice (Luz et al. 1985 Muller et al. 1978). 

The 5, 8-cyclonucleosides are now recognized as significant oxidative lesions that are chemically stable and form in mammalian DNA in vivo. In pig liver DNA, the levels of (5 5)-5, 8-cyclo-dA ( 0.7 lesions/10 DNA bases) were approximately four-to seven-fold lower than the levels of 8-oxo-dG, but were approximately three-fold higher than levels of 8-oxo-dA. Elevated levels of (5 S)-5, 8-cyclo-dA have also been observed in the breast connective tissue stroma of women between 33 and 46 years of age, which correlates with the known sharp increase in breast cancer incidence for women of this age group. 

However, because chronic-duration exposure to 2,3-benzofuran increases the incidence of cancer in rodents, including liver cancer in mice (NTP 1989), any possible anticarcinogenic action of 2,3-benzofuran is less relevant. 

Fig. 8.6 Estimated risk of liver cancer, P(d), in relation to dose of aflatoxin, d, as determined with different dose-incidence models. The models for the different curves. are as follows OH. one-hit model MS, multi-stage model W, Weibull model MH, multihit model MB, Mantel-Bryan (log-probit model) (from Krewski and Van Ryzin, 1981).

Vinyl chloride causes liver cancer (hemangiosarcoma), narcosis, and Raynaud s phenomenon that comprises scleroderma, acro-osteolysis, and liver damage. The appearance of liver tumors is dose dependent but reaches a maximum at about 22% incidence. This seems to be due to the fact that the metabolism that is necessary for the carcinogenicity, is saturated, and/or inhibited by vinyl chloride. The toxic metabolites produced are the epoxide and chloroacetaldehyde. 

The most common type of primary liver tumor is hepatocellular carcinoma other types include cholangiocarcinoma, angiosarcoma, glandular carcinoma, and undifferentiated liver cell carcinoma. Although a wide variety of chemicals are known to induce liver cancer in laboratory animals (Table 14.1), the incidence of primary liver cancer in humans in the United States is very low. 

An elevated incidence of liver cancer has been seen in the first series of German patients (6 versus 1.1 to 1.2 expected). Five cases of kidney cancer have also been observed, compared with 2.4 to 2.6 expected (Spiess et al. 1989) however, this increase is not statistically significant. The authors suggest that these cancers may also have been induced by the radium-224. 

All of the seeming paradoxes above can be resolved by remembering the difference between prediction and postdiction. You should be astonished if someone tells you in advance that you will pick the three of spades, the six of diamonds, and the eight of diamonds. You should be concerned if a town with a factory which produces a known liver carcinogen shows a statistically significant incidence of increased liver cancer. And if anyone can tell you for sure that the lottery ticket you are about to purchase will be a winner, by all means do it. 

Bi and Gi are the most highly toxic and are animal carcinogens. Bi is teratogenic in rodents. In countries where food contains aflatoxins, there is an increased incidence of liver cancer. Listed as known human carcinogens.3... 

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