Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of protein deficiency on the hepatotoxicity and carcinogenicity of sterigmatocystin was studied in rats. Sterigmatocystin, 500 ppm/day, fed in a regular diet induced marked toxic effects and there was a high incidence of hepatocellular carcinoma and hyperplastic nodules. The same dosage fed in a protein-deficient diet produced toxic signs followed by a high incidence of death within 27 weeks. Surviving animals showed dysplastic liver cell changes but no tumors were noted. The incidence of hepatocellular carcinoma was 87% in rats receiving 15 ppm of the substance per day for 200 days in a protein-deficient diet. Sequential histologic and histochemical studies revealed that hyperplastic and preneoplastic liver lesions appeared at 28--32 weeks after inseption of the sterigmatocystin-supplemented diet. No cirrhotic changes and only transient fibrosis were noted. The morphogenesis of the sterigmatocystin-induced lesions was compared with that of aflatoxin B1-induced lesions.
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PMID:Sequential hepatic changes during sterigmatocystin-induced carcinogenesis in the rat. 4 22

Three of 42 (7%) monkeys given aflatoxin B1 (AFB1) for longer than 2 years have developed primary malignant neoplasms of the liver. Liver biopsies performed at intervals during aflatoxin administration revealed that neoplasia was preceded by pathologic lesions of the liver, including toxic hepatitis, proliferation of pseudotubules, and hyperplastic nodules. Serum alpha-fetoprotein levels, monitored in one of the monkeys by radioimmunoassay, paralleled tumor growth and recurrence of the hepatocellular carcinoma. Normal serum alpha-fetoprotein levels were noted for a monkey with hemangioendothelial sarcoma. Our results implicate AFB1 as a liver carcinogen in monkeys and add additional support to the hypothesis that humans exposed to this substance may be at risk of developing liver cancer.
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PMID:Carcinogenicity of aflatoxin B1 in rhesus monkeys: two additional cases of primary liver cancer. 6 57

During induction of hepatocellular carcinoma (HCC) in rats with 3'MeDAB (3'methyl-dimethyl-aminoazobenzene) and Aflatoxin B1 alpha-foetoprotein (AFP) could already be demonstrated in the serum in the early phase of carcinogen administration. In this period the liver showed livercell necrosis but no tumour formation. The AFP level in the induction phase was correlated with the degree of livercell necrosis. The detection of AFP during the induction period is of importance as it is followed by a high frequency of liver tumours in later phases. The AFP concentration in the tumour phase was not related in any histological feature of the tumour; however, the mean AFP concentration in cases of HCC combined with cirrhosis was much higher than in cases of HCC without cirrhosis. Some rats with HCC showed AFP-negative sera, but AFP-positive bile.
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PMID:Alpha-foetoprotein during chemically induced hepatocellular carcinoma in rats. 8 43

Herpesvirus saimiri (HVS) is an oncogenic virus for a variety of nonhuman primates. HVS does not produce overt disease upon inoculation in the natural host (squirrel monkey) but consistently induces neoplasms including lymphomas and lymphocytic leukemias in 4 other species of monkeys. Various drugs inhibit replication of HVS in vitro including cytosine arabinoside and adenine arabinoside. In addition, the lymphoma and leukemia induced in owl monkeys responds to vincristine and prednisolone, cyclophosphamide, cytosine arabinoside, and human interferon. Of the various chemical carcinogens studied, the antitumor agent procarbazine induces neoplasms in a variety of species including monkeys. Thus far this compound has induced acute myelogenous leukemia (AML), lymphoma, and hemangiosarcomas in macaques. We have induced primary liver tumors in macaques with several nitrosamines and aflatoxin B1 and these tumors produce alpha-fetoprotein (AFP) which can be assayed for both diagnosis and therapy. Thus far, therapy of hepatocellular carcinoma has been most successful with surgical resection; and the tumor mass and serum AFP have been less responsive to single agent chemotherapy. These nonhuman primate models are useful for an understanding of the cause, diagnosis, prevention, and treatment of the human disease.
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PMID:Nonhuman primate models for lymphoma, leukemia, and other neoplasms. 16 36

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.
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PMID:Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1. 17 84

The epidemiological studies suggest that aflatoxins, the toxic metabolites of the ubiquitous mold Aspergillus flavus, may play a significant role in the evolution of hepatocellular carcinoma in man in certain geographic areas of the world. To ascertain their carcinogenicity in nonhuman primates, we have administered highly purified aflatoxin B1, intermittently in the diet at 2 ppm, to 10 female and 8 male tree shrews. The tree shrew (Tupaia glis) is a nonhuman primate occurring throughout Southeast Asia which can be reared easily in captivity. Of 12 animals that survived, 6 of 6 female (100%) and 3 of 6 male (50%) tree shrews developed hepatocellular carcinomas between 74 and 172 weeks after the beginning of the experiment. None of the 8 control animals developed liver cancers. The estimated total amount of aflatoxin B1 consumed by these animals ranged from 24 to 66 mg. The development of liver tumors did not follow a specific pattern; considerable variation in hepatocellular responses to aflatoxin B1 was noted in these animals. In 2 tree shrews, the liver tumors were associated with severe post necrotic scarring; in the other 7 tumor-bearing livers, only mild to moderate portal fibrosis was encountered. This individual variation in hepatocellular response and in the amount of aflatoxin B1 required to induce hepatocellular carcinomas is attributed to inherent differences in the susceptibility within a given species of outbred animals and suggests extreme caution in proposing the "permissible" or "safe" levels of contamination of carcinogens in the food-stuffs.
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PMID:Induction of liver tumors by aflatoxin B1 in the tree shrew (Tupaia glis), a nonhuman primate. 17 5

A study has been made of changes occurring in rat liver nuclei as a result of the chronic and acute administration of aflatoxin B1. This has involved resolution of the nuclei into populations of differing ploidy by means of centrifugation in a zonal rotor. Chronic feeding of the toxin to weanling rats prevents the development of the predominant tetraploid hepatocyte nuclear population, which normally takes place during maturation. Increased populations of diploid and octaploid hepatocyte nuclei are observed. Chronic feeding of the toxin to adult animals also causes a reduction in the tetraploid population already established and, again, leads to increased numbers of diploid and octaploid nuclei. Once an abnormal nuclear population has been established by feeding the toxin, it persists until the development of hepatocarcinoma (if a 6-week carcinogenic feeding regimen has been used). The hepatomas have diploid nuclei. Labeling hepatic RNA and DNA in vivo has indicated that feeding the toxin causes a reversion to the immature distribution of DNA synthesis among the nuclear population, with little effect on the pattern of distribution of RNA synthesis. Acute administration of aflatoxin to adult rats also causes a reduction in the size of the tetraploid population, with increased proportions of diploid, octaploid, and higherploidy nuclei. These results are discussed in terms of a dual action of the toxin, antimitotic and necrogenic, and the possible relationship of these to the carcinogenic process.
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PMID:Some effects of acute and chronic dosing with aflatoxin B1 on rat liver nuclei. 17 33

The sequential development of lesions in the liver leading to hepatocellular carcinoma in experimental animals appears to follow a similar pattern irrespective of the carcinogen. The speed with which the lesions develop is related to the chemical, the dose and dosing schedule, and the diet fed. In studies with aflatoxin B1 there is a predictable series of morphological expressions beginning with focal areas of hydropic degeneration (Stage 1); hyperplastic basophilic cells, singly or in close association with Stage 1 (Stage 2); nodular hyperplasia of parenchymal cells which become progressively more abnormal (Stage 3); transitional cell changes (Stage 4); and, ultimatley, hepatocellular carcinoma (Stage 5).
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PMID:Experimental hepatocellular carcinogenesis. 17 4

We examined whether hormones would modify the carcinogenic action of aflatoxin B1 (AFB1). Four groups of inbred Fischer rats received AFB1, 125 mug per animal, weekly per os. In three of the groups, certain hormones were administered simultaneously: One group received 1 U growth hormone (GH) sc weekly, another was given 4 U adrenocorticotropin (ACTH) weekly, and a third received 0.5 U insulin weekly sc. AFB1, ACTH, and insulin were given for 20 weeks; GH was given for only 10 weeks. The control group did not receive hormone adjuvant. In each group, 4 animals were killed at 7, 14, 21, 28, and 35 weeks; the remaining rats were killed at 77 weeks. Their livers were carefully examined and samples prepared for light and electron microscopy. Animals receiving AFB1 and ACTH failed to exhibit hepatocellular carcinoma. On the other hand, malignant lymphoma appeared at 56 weeks in 3 of the 6 surviving males on this regime. AFB1, alone or when given with insulin or GH, caused hepatocellular carcinoma in all animals; in these, lymphoma was not observed. Lymphoma comprised two cell types, each with similar neclear characteristics but differing in their nucleocytoplasmic ratios and in the amount and distribution of cytoplasmic organelles. Alterations leading to hepatocellular carcinoma were examined at various stages of development. "Basophilic hyperplasia" reflected an increase in free ribosomes. "Hyperplastic nodules" were composed of hepatocyte aggregates with characteristics similar to those encountered in the earlier stage. Both the "neoplastic nodules" and hepatocellular carcinomas were formed by cells containing large, "smooth fingerprints" and free ribosomal aggregates. These features supported the concept that AFB1 impairs ribosomal binding to endoplasmic reticulum membranes. The failure of ACTH-treated animals to develop hepatocellular carcinoma was ascribed to the effect of adrenal cortical stimulation upon membrane-polysome binding.
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PMID:Inhibition of hepatocarcinogenesis by adrenocorticotropin in aflatoxin B1-treated rats. 18 49

Diets containing either 49.5% or 32% casein or fish protein concentrate (FPC) were fed to young rainbow trout (Salmo gairdneri) for 12 months. Five levels [0, 2, 6, 18, and 54 parts per billion (ppb)] of aflatoxin B1 (AFB1) were given in each of four different diets. A 30-fish sample was taken at 6, 9, and 12 months to determine the influence of diet on the carcinogenicity of AFB1. Both levels of casein produced similar hepatoma incidences at each level of AFB1. The diet high in FPC produced more tumours than did the casein diets at 2, 6, and 18 ppb AFB1, whereas fish fed the diet low in FPC had a significantly (P less than 0.05) lower hepatoma incidence than did the other three groups. The liver size (percent body wt) was smaller at higher toxin levels in all instances. The growth of fish given 32% casein was less than that of the other groups.
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PMID:Effect of dietary protein on the response of rainbow trout (Salmo gairdneri) to aflatoxin B1. 20 15


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