Dissimilar Frequency of Hepatoblastomas and Hepatic Cystadenomas and Adenocarcinomas Arising in Hepatocellular Neoplasms of D2B6F1 Mice Initiated with N-Nitrosodiethylamine and Subsequently Given Aroclor-1254, Dichlorodiphenyltrichloroethane, or Phenobarbital

Abstract

Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to phenobarbital (PB) for their ability to promote hepatocellular proliferative lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular neoplasms developed in all mice given NDEA and were more numerous in mice fed promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB was the most effective of the 3 agents in stimulating the evolution of hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast, lesions resembling benign and malignant cholangiocellular neoplasms were frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal metaplasia/cholangiocellular tumor morphology appear to constitute different patterns of genetic programming induced by certain promoters in expanding clones of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1 male mice.

Does Mortality Risk of Cigarette Smoking Depend on Serum Concentrations of Persistent Organic Pollutants? Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study

“…POPs are lipophilic chemicals that accumulate in adipose tissue and are associated with the risk of various chronic diseases [7], [8], [9]. The biological plausibility for our hypothesis was that experimental studies in mice reported that pretreatment with some POPs increased toxicity of important chemicals contained in cigarette smoke, like benzopyrene, dimethylnitrosamine, and N-nitrosodiethlyamine [10], [11].…”

Associations between Cigarette Smoking and Total Mortality Differ Depending on Serum Concentrations of Persistent Organic Pollutants among the Elderly

“…More than 3,000 chemicals have been identified in cigarette smoke, and many of them are both mutagenic and carcinogenic. Experimental findings on increased carcinogenicity of chemicals contained in cigarette smoking after pretreatment of some POPs strongly suggest the biological interaction between cigarette smoking and POPs (6, 7). …”

“…In experimental studies, pretreatment of PCBs or some OCPs like DDT increased genotoxicity of carcinogens like benzopyrene, dimethylnitrosamine, and N-nitrosodiethylamine, which are important components of cigarette smoke (6, 7). In fact, the chronic exposure to low dose POPs has recently been linked to various common diseases in general population (8-12).…”

Polychlorinated Biphenyls and Polybrominated Biphenyls

“…After 2.5 weeks, mice were given Aroclor 1254 as an intraperitoneal dose at 0 (tricaprylin/corn oil, 1/4, v/v) Diwan et al (1994) examined whether Aroclor 1254 promoted NDEA-initiated tumours of the liver in groups of 30 male DBA/2NCr × C57BL/6NCr (D2B6F1) mice. At age 5 weeks, mice were injected intraperitoneally with NDEA at a dose of 0 (tricaprylin vehicle) or 90 mg/kg bw.…”