Biomedical subjects

S Hendrich

Publications and source records attributed to S Hendrich.

43 records · Page 3Linked to original sources

PubMed1988

Gene expression during multistage hepatocarcinogenesis.

Several multistage models of hepatocarcinogenesis in the rat have now been developed. In one of these models at least three distinct stages--initiation, promotion, and progression--can be delineated. The first and last are irreversible, while that of promotion is reversible. Quantitation of each stage is possible. While several variable marker enzymes have been utilized to identify and characterize preneoplastic lesions during the stage of promotion, preliminary investigations indicate that the transcriptional activation of proto-oncogenes, particularly that of c-raf-1 proto-oncogene, may be used as an indicator of those preneoplastic lesions that will potentially develop into malignant neoplasms.

Animals↗

PubMed1987

Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis.

Enzymes of glutathione metabolism, particularly gamma-glutamyltransferase (GGT) and glutathione S-transferase (GST), play a role in multistage hepatocarcinogenesis. The enhanced expression of these enzymes in preneoplastic altered hepatic foci, nodules, and hepatocellular carcinomas has been demonstrated after treatment with a variety of initiating and promoting agents. Glutathione is necessary for the detoxification of xenobiotics and carcinogens and for cell replication. Induction of GGT in altered hepatocytes may permit these cells to utilize extracellular glutathione to preserve their internal glutathione levels. GST induction allows glutathione utilization for the protection of the altered hepatocyte in an environment of exposure to xenobiotics, such as promoting agents. Thus, the combined effects of GGT and GST, in a toxic environment, may provide for the enhanced proliferation observed in preneoplastic hepatocytes. New clinical and research opportunities may involve the use of GGT and the placental isozyme of GST (PGST) as markers of preneoplasia and neoplasia in humans. Many factors, such as hormones, diet, and exposure to initiating and promoting agents, influence GGT and GST expression. The recent cloning of cDNAs to GGT and PGST offers opportunities for the study of factors involved in the genetic expression of these two enzymes. Coupled with the use of hepatocyte culture and transplantation, the factors involved at the molecular level in the creation of hepatocellular neoplasia may be discovered.

Animals↗

PubMed1987

Quantitative stereological evaluation of four histochemical markers of altered foci in multistage hepatocarcinogenesis in the rat.

Female F344/N rats dosed with diethylnitrosamine (DEN) 24 h after partial hepatectomy were treated with the promoting agents, phenobarbital (PB) or 3,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or the peroxisome proliferating agent, WY 14,643, for 6 months. Another group was subjected to the Solt-Farber protocol. Altered hepatic foci (AHF) were analyzed by quantitative stereology from frozen serial sections stained for gamma-glutamyl transferase (GGT), canalicular adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6Pase) and the placental isozyme of glutathione S-transferase (PGST). PGST scored more foci in all groups than GGT and ATPase. PGST marked greater focal volume than GGT or ATPase, and PGST marked focal volume equal to or greater than G6Pase in rats treated with PB, TCDD or the Solt-Farber protocol. However, after treatment with WY 14,643, GGT and PGST marked much less focal volume than ATPase or G6Pase, and PGST scored fewer foci than G6Pase. Numerical estimations of foci scored by those markers on the basis of area of the entire tissue section (per cm2) were relatively different from those values determined by quantitative stereology. While these results confirm earlier studies, they demonstrate the importance of quantitative stereologic analysis of AHF during multistage hepatocarcinogenesis.

Adenosine Triphosphatases↗

PubMed1986

Effects of dietary Schizandra chinensis, brussels sprouts and Illicium verum extracts on carcinogen metabolism systems in mouse liver.

Ethanol extracts of Brussels sprouts (BRX), Schizandra chinensis (SZX) or Illicium verum (IVX) were added to a semi-purified basal diet and fed to adult male and female C57B1/6 mice for 14 and 10 days, respectively. Other groups received the unsupplemented basal diet or a mouse chow. Liver fractions were prepared from these mice to investigate the effects of the diets on the enzyme systems involved in benzo[a]pyrene (BP) and aflatoxin B1 (AFB1) metabolism. The effects of the microsomal or cytosolic liver fractions on the in vitro mutagenicity of BP and AFB1 and on the DNA binding of AFB1 were also studied. There were several apparently sex-related differences in the responses of the monooxygenase system components measured. In males, cytochrome P-450 levels were significantly increased only in the chow group, while significant increases in both 7-ethoxycoumarin O-deethylase (ECD) and aryl hydrocarbon hydroxylase (AHH) activities were seen only in the SZX group. In females, cytochrome P-450 levels were significantly increased in both the BRX and SZX groups, whereas AHH activity was significantly increased only in the chow and BRX groups and ECD activity was increased in the SZX and IVX groups. Microsomal epoxide hydratase (EH) was induced in males in the SZX and IVX groups and in females only in the SZX group, while cytosolic EH was significantly increased only in IVX males. Diet-induced changes in monooxygenase activities were found to be the best indicators of changes in microsome-mediated BP mutagenesis and AFB1 mutagenesis and binding to DNA in vitro, with a direct correlation between high AHH and/or ECD activities and the levels of mutagenic response to BP or AFB1 in the Ames assay and of DNA binding of AFB1.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1986

The phenotypic stability of altered hepatic foci: effects of withdrawal and subsequent readministration of phenobarbital.

Previous studies from this and a number of laboratories have demonstrated that the majority of both focal and nodular lesions which occur during the early phase of multistage hepatocarcinogenesis in the rodent disappear or 'remodel' upon removal of the promoting agent. Utilizing techniques of quantitative stereology we have found that many if not the majority of altered hepatic foci induced by initiation with diethylnitrosamine/partial hepatectomy and promoted for 4 months with phenobarbital disappear with little or no morphologic evidence of remodeling within 10 days after withdrawal from phenobarbital and do not reappear for a 6-month period thereafter. However, administration of phenobarbital in the diet following an interval period of 10, 20, 30 or 90 days in the absence of the promoting agent resulted in the reappearance of these focal lesions at the same or an increased numerical level. The volume occupied by these focal lesions, which reflects the total numbers of altered cells present in the liver, increased somewhat even during the interval absence of phenobarbital but increased dramatically upon readministration of the promoting agent. Rats fed only a semi-purified diet for 180 days following a 4-month period of phenobarbital promotion of initiated animals exhibited a greater number but only half the total volume of altered hepatic foci, as did rats fed a cereal-based diet only for 180 days. The cereal-based diet (NIH-07) may contain some unknown initiating and/or promoting factors responsible for this phenomenon. These studies present further evidence both for the reversible nature of the stage of promotion of hepatocarcinogenesis and the irreversible characteristic of the stage of initiation, as well as the importance of the composition of the diet utilized in models of multistage hepatocarcinogenesis.

Animals↗

PubMed1983

Effects of dietary cabbage, Brussels sprouts, Illicium verum, Schizandra chinensis and alfalfa on the benzo[alpha]pyrene metabolic system in mouse liver.

Male C57B16 mice were fed on diets containing either 20% cabbage, 20% Brussels sprouts, 20% alfalfa, 5% Schizandra chinensis or 5% Illicium verum (two Chinese medicinal herbs) or on a chow or purified basal diet for 14 days after a 1-wk equilibration period on the basal diet. Liver microsomal fractions were assayed for cytochrome P-450 content, aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH). Liver microsome-mediated benzo[a]pyrene (BP) metabolism (with and without an EH inhibitor, 1,2-epoxy-3,3,3-trichloropropane) was analysed by HPLC. Liver weights of the animals fed on Brussels sprouts and I. verum were significantly increased compared with those of the animals fed on basal diets. S. chinensis induced a 3-fold increase in cytochrome P-450 (P less than 0.05). Although P-450 induction in the other groups was as high as 1.8-fold (for chow), statistical significance was not established. Chow induced AHH activity 2.2-fold (P less than 0.05), while S. chinensis and alfalfa induced 1.6-fold and 1.7-fold increases, respectively, in AHH activity, although neither increase was statistically significant. EH was stimulated significantly in the following order: I. verum (2.1-fold) greater than chow (1.7-fold) greater than S. chinensis (1.6-fold) greater than Brussels sprouts (1.4-fold). Total levels of BP metabolism and phenol II (primarily 3-hydroxybenzo[a]pyrene) formation were closely associated for each dietary treatment. Total BP metabolism was significantly increased (2.1-fold) in the chow-fed group and increased 1.6-fold in the S. chinensis group (P greater than 0.05). No increase was seen with the other diets. Phenol II formation relative to total metabolites was significantly increased for the S. chinensis and I. verum groups compared to the basal group. Diet-related variations in phenol production relative to total metabolism were eliminated by addition of the EH inhibitor to the incubation media.

Animal Feed↗

PubMedDate not supplied

Dietary agents in cancer prevention: flavonoids and isoflavonoids.

Flavones and isoflavones may play a prominent role in cancer prevention since these compounds are found in numerous plants that are associated with reduced cancer rates. This article reviews recent epidemiological and animal data on isoflavones and flavones and their role in cancer prevention. It covers aspects of the bioavailability of these dietary constituents and explores their mechanism of action. Human epidemiology data comes primarily from studies in which foods rich in isoflavones or flavones are associated with cancer rates. This approach has been particularly useful with isoflavones because of their abundance in specific foods, including soy foods. The bioavailability of flavones and isoflavones has been shown to be influenced by their chemical form in foods (generally glycoside conjugates), their hydrophobicity, susceptibility to degradation, the microbial flora of the consumer, and the food matrix. Some information is available on how these factors influence isoflavone bioavailability, but the information on flavones is more limited. Many mechanisms of action have been identified for isoflavone/flavone prevention of cancer, including estrogenic/antiestrogenic activity, antiproliferation, induction of cell-cycle arrest and apoptosis, prevention of oxidation, induction of detoxification enzymes, regulation of the host immune system, and changes in cellular signaling. It is expected that some combination of these mechanisms will be found to be responsible for cancer prevention by these compounds. Compelling data suggest that flavones and isoflavones contribute to cancer prevention; however, further investigations will be required to clarify the nature of the impact and interactions between these bioactive constituents and other dietary components.

Animals↗