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

Differences in the distribution of phenotypic alterations in initiated and promoted cell populations reflect both the dose and the action of the specific initiating agent, as well as the mechanism of action of the promoting agent. The use of multiple phenotypic markers to characterize AHF should allow further experimentation on the characteristics of promoting agents in hepatocarcinogenesis, especially their ability to promote separate populations of initiated cells, and on those characteristics of initiated cells that enable certain ones to survive and multiply in the specific environment provided by a promoting agent. Studies of promoting agents with differing mechanisms of action should further allow questions of reversibility, substitution and additivity of the actions of promoting agents to be addressed. The possibility that individual promoting agents do not enhance the growth of the entire population of initiated cells indicates that study of combinations of promoting agents is an important future direction of research. Therefore, information on the characteristics of promoting agents, singly and in combination, is necessary to assess more accurately the contribution of promoting agents to the carcinogenic risk for humans distinct from the effects of initiating agents and complete carcinogens.
Carcinogenesis 1992 May
PMID:The role of the stages of initiation and promotion in phenotypic diversity during hepatocarcinogenesis in the rat. 158 86

The use of AHF in the rat as a predictive lesion for carcinogenesis has been frequently suggested. Regulatory agencies require that the data used to determine carcinogenic potential and for estimating risk cannot be open to different interpretations. The degree of uncertainty in establishing relationships between the different foci phenotypes, their fate, and the difference in results with different protocols precludes the use of these data is establishing carcinogenic hazard or in quantitative risk estimation.
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PMID:Altered hepatic foci in rat liver as weight of evidence of carcinogenicity: the Canadian perspective. 262 2

Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.
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PMID:A 2-year dose-response study of lesion sequences during hepatocellular carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical dichloroacetic acid. 1251 79

Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3(rd) week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P(+) AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group.
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PMID:Sewage sludge does not induce genotoxicity and carcinogenesis. 2305 6