Carcinogenicity of iron in conjunction with a chlorinated environmental chemical, hexachlorobenzene, in C57BL/10ScSn mice.
Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB) (Smith and Francis, 1983). HCB will also cause liver tumours in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers. To determine whether iron overload will potentiate the hepatocarcinogenicity of HCB, male C57BL/10ScSn mice received a single dose of iron-dextran complex or the dextran carrier and were then fed HCB in the diet (0.01%) for up to 18 months. A very clear potentiation by iron of liver tumour incidence occurred. Of the mice which received HCB, but no iron, for 12 months a low incidence of liver hyperplastic nodules was observed, whereas preadministration of iron increased the incidence. After 18 months, all surviving mice initially given iron followed by HCB developed advanced hepatic nodules and 90% had hepatocellular carcinomas. No tumours were seen in animals that only received HCB. Nodules were not seen in iron-dosed mice receiving control diet, but another novel observation was that these animals developed porphyria by 6 months. Although iron enhanced tumour formation in the presence of HCB, the foci, nodules and carcinomas formed all excluded iron. Preliminary studies with the DBA/2 strain suggested that these mice were considerably less susceptible to potentiation by iron.
Smith
A G
AG
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK.
Cabral
J R
JR
Carthew
P
P
Francis
J E
JE
Manson
M M
MM
D000818:Animals; D002722:Chlorobenzenes / Q000633:toxicity*; D004357:Drug Synergism; D006581:Hexachlorobenzene / Q000633:toxicity*; D006984:Hypertrophy / Q000139:chemically induced; D007501:Iron / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009336:Necrosis; D011164:Porphyrias / Q000139:chemically induced
D002722:Chlorobenzenes; D006581:Hexachlorobenzene; D007501:Iron