Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dinophysistoxin-1, 35-methylokadaic acid, is a causative agent of diarrhetic shellfish poisoning. The biological activities and tumor-promoting activity of dinophysistoxin-1 were studied together with those of okadaic acid and 7-O-palmitoyl okadaic acid. Dinophysistoxin-1 is a skin irritant and induces ornithine decarboxylase in mouse skin with the same potency as okadaic acid. 7-O-Palmitoyl okadaic acid induced a lower activity than the other compounds. Dinophysistoxin-1 inhibited the specific [3H]okadaic acid binding to a particulate fraction of mouse epidermis. The binding affinities of dinophysistoxin-1 and okadaic acid to a particulate fraction were almost the same. Dinophysistoxin-1 showed a tumor-promoting activity as strong as that of okadaic acid in a two-stage carcinogenesis experiment on mouse skin. The percentages of tumor-bearing mice in the groups treated with 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) followed by 5 micrograms of dinophysistoxin-1, twice a week, and with DMBA followed by 5 micrograms of okadaic acid twice a week were 86.7% and 80.0% in week 30, respectively. The average number of tumors per mouse was 4.6 in the former group and 3.9 in the latter. Dinophysistoxin-1 and okadaic acid act on cells through different pathways from the 12-O-tetradecanoylphorbol-13-acetate-type tumor promoters.
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PMID:Diarrhetic shellfish toxin, dinophysistoxin-1, is a potent tumor promoter on mouse skin. 314 97

Peroxisome proliferator hepatocarcinogens lack genotoxic activity in numerous in vitro assays using non-target cells which do not respond with peroxisome proliferation. Therefore, the effect of in vivo treatment with WY-14,643 on DNA repair was quantitated in rat hepatocytes, the target cell for carcinogenesis. Palmitoyl CoA oxidase and carnitine acetyltransferase activities in isolated hepatocytes were elevated by WY-14,643 (50 mg/kg/day by gavage for up to 5 consecutive days) and by WY-14,643 (0.1%) or di(2-ethyl-hexyl)phthalate (DEHP) (1.2%) feeding (for up to 28 days), indicating peroxisome proliferation had occurred. DNA repair as unscheduled DNA synthesis (UDS) was measured autoradiographically as net nuclear grains following thymidine incorporation in primary hepatocyte cultures. Treatment of rats with WY-14,643 (gavage or feeding) or DEHP (feeding) did not induce UDS. Addition of 2-acetylaminofluorene to replicate cultures demonstrated that WY-14,643 or DEHP treatment did not prevent repair response. Additional cultures were treated with H2O2 (0.8 mM H2O2 3x at 1-h intervals) to evaluate the ability of UDS to detect any repair which may be induced by peroxisomal metabolism. H2O2 did not induce UDS at this concentration, nor did it prevent 2-acetylaminofluorene-induced repair. UDS was, however, observed in a separate experiment using a higher concentration of H2O2. In summary, a highly carcinogenic peroxisome proliferator did not induce UDS in the target cell for carcinogenesis in spite of peroxisome proliferation following in vivo treatment.
Carcinogenesis 1988 Jul
PMID:Failure of the peroxisome proliferator WY-14,643 to induce unscheduled DNA synthesis in rat hepatocytes following in vivo treatment. 338 37

Peroxisome proliferators are well known to cause liver enlargement in rodents. In this investigation, we have examined the effect of acute (1 week) and chronic (26 week) exposure to the peroxisome proliferators methylclofenapate (MCP) and clofibric acid (CA), at 0.05 and 0.5% in the diet respectively, on hepatocyte replication in the Sprague-Dawley rat. Both compounds induced an early increase in hepatocyte replication, with a concomitant increase in peroxisome proliferation as assessed by induction of palmitoyl CoA oxidation. However, after 26 weeks of treatment, there was no difference in the labelling index (LI) of control and CA-treated rat livers, while in MCP-treated rats the LI was 5- to 6-fold above control. Palmitoyl CoA oxidation remained elevated in both treated groups at 26 weeks. Analysis of the slides by a 'zonal' scoring procedure demonstrated that the induced replication was predominantly periportal after 1 week of treatment with either compound. The number of 5-bromo-2'-deoxyuridine (BrdU)-positive hepatocyte nuclei per field in the periportal region increased approximately 4-fold after CA treatment and 7-fold after MCP treatment. There was no significant difference in the number of BrdU-positive nuclei per field in the centrilobular areas of control and treated rats after 1 week. After 26 weeks of treatment, periportal replication was still elevated in the MCP-treated animals (approximately 10-fold above control), but there was no difference in periportal replication between control and CA-treated rats. CA induced a significant reduction in the replication of centrilobular areas at 26 weeks, while there was no effect of MCP. In summary, these results demonstrate that the acute mitogenic effects of MCP and CA are predominantly periportal, and, in the case of MCP, the mitogenicity is sustained up to 26 weeks of treatment.
Carcinogenesis 1993 Jul
PMID:Comparison of the acute and chronic mitogenic effects of the peroxisome proliferators methylclofenapate and clofibric acid in rat liver. 833 Mar 63