{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:50:17Z","timestamp":1791435017086,"version":"4.3.3"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,1,11]],"date-time":"2006-01-11T00:00:00Z","timestamp":1136937600000},"content-version":"vor","delay-in-days":4089,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[1994,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The chronic dietary administration of hexachlorobenzene (HCB) to rats for a year or more results in the formation of liver tumours described as hepatocellular carcinomas, hepatomas or haemangiomas. The hepatotoxicity of HCB, which is greatest in hamsters and rats, gives rise to peliosis and necrosis with haemosiderosis. This pattern of hepatotoxicity indicates vascular damage, which through haemosiderosis could increase not only the toxic effect of HCB to hepatocytes but also its tumourogenic potential. The present study confirmed vascular damage by the identification of widespread fibrin deposits in the livers of rats chronically exposed to HCB, using an antibody to rat fibrin. Based on our study we suggest that the formation of hepatomas and haemangiomas with elements of peliosis (cystic blood\u2010filled cavities) could be explained by the compensatory hyperplastic responses to hepatocellular necrosis and by the simultaneous loss of hepatocellular cords. The accumulation of iron in the liver would strongly potentiate the development of hepatic tumours, as has been found in HCB and polychlorinated biphenyl\u2010treated mice with iron overload. The implications of this non\u2010genotoxic mechanism of hepatoma formation for the assessment of human health risk are discussed.<\/jats:p>","DOI":"10.1002\/jat.2550140610","type":"journal-article","created":{"date-parts":[[2006,10,16]],"date-time":"2006-10-16T05:15:29Z","timestamp":1160975729000},"page":"447-452","source":"Crossref","is-referenced-by-count":25,"title":["Pathological mechanisms of hepatic tumour formation in rats exposed chronically to dietary hexachlorobenzene"],"prefix":"10.1002","volume":"14","author":[{"given":"P.","family":"Carthew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. G.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/269510a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910230110"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(80)90108-1"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910430325"},{"key":"e_1_2_1_6_2","first-page":"203","article-title":"Iron\u2010enhancement of the hepatic porphyria and cancer induced by environmental polyhalogenated aromatic chemicals","volume":"76","author":"Smith A. G.","year":"1989","journal-title":"Adv. Biosci."},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/11.3.437"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1988.tb55510.x"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/14.7.1381"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/6.4.631"},{"key":"e_1_2_1_11_2","first-page":"417","article-title":"Oncogenicity of hexachlorobenzene","volume":"77","author":"Erturk E.","year":"1986","journal-title":"IARC Sci. Publ."},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098588902600607"},{"key":"e_1_2_1_13_2","first-page":"1099","article-title":"Histogenesis of malignant liver tumours induced by dimethylnitrosamine. An experimental study of Syrian hamsters","volume":"39","author":"Herrold K.","year":"1967","journal-title":"J. Natl. Cancer. Inst."},{"key":"e_1_2_1_14_2","first-page":"147","article-title":"Hemangiomatous lesions of mice treated with nitrosodimethylamine","volume":"62","author":"Otsuka H.","year":"1971","journal-title":"Gann"},{"key":"e_1_2_1_15_2","first-page":"465","article-title":"Malignant tumours induced in mice fed with N\u2010nitrosodimethylamine","volume":"54","author":"Takayama S.","year":"1963","journal-title":"Gann"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1966.100"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1956.15"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711580211"},{"key":"e_1_2_1_19_2","first-page":"1489","article-title":"Neoplastic nature of the liver \u201cblood cysts\u201d induced by urethane in mice","volume":"31","author":"Trainin N.","year":"1963","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9975(08)80042-4"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9975(08)80200-9"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/264440a0"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711510206"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840090609"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199002000-00006"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840050622"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840110512"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7291981"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1177\/096032718800700505"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.2550140610","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.2550140610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T16:18:16Z","timestamp":1760545096000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.2550140610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,11]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1994,11]]}},"alternative-id":["10.1002\/jat.2550140610"],"URL":"https:\/\/doi.org\/10.1002\/jat.2550140610","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,11]]}}}