Search for Ha-ras codon 61 mutations in liver tumours caused by hexachlorobenzene and Aroclor 1254 in C57BL/10ScSn mice with iron overload.
C57BL/10ScSn mice administered iron--dextran and fed the environmental pollutants hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) develop hepatic nodules and carcinomas within 18 months. A range of lesions from the livers were analysed for the presence of mutations in the Ha-ras proto-oncogene at codon 61 using the polymerase chain reaction to amplify DNA from formalin-fixed sections, followed by oligonucleotide hybridization. Only two mutations from 23 preneoplastic and neoplastic lesions induced by HCB were detected (a focus of altered cells and a trabecular cell carcinoma). With Aroclor 1254 no mutations were detected in 28 areas at various stages of carcinogenesis analysed. Sequencing of the two mutations generated by HCB showed a C-->T transversion at the first base of codon 61 (carcinoma) and an A-->T transversion at the second base (proliferative focus). Thus, in marked contrast to some other systems of mouse liver tumour induction, hepatocarcinogenesis caused by HCB and PCBs in C57BL/10ScSn mice is an example of carcinogenesis which does not involve a high frequency of Ha-ras gene mutation at codon 61.
Rumsby
P C
PC
BIBRA, Carshalton, Surrey, UK.
Evans
J G
JG
Phillimore
H E
HE
Carthew
P
P
Smith
A G
AG
D000818:Animals; D001140:Aroclors / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D020111:Chlorodiphenyl (54% Chlorine); D003043:Cocarcinogenesis; D003062:Codon / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics*; D006581:Hexachlorobenzene / Q000633:toxicity*; D007501:Iron / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016133:Polymerase Chain Reaction
D001140:Aroclors; D002273:Carcinogens; D003062:Codon; D020111:Chlorodiphenyl (54% Chlorine); D006581:Hexachlorobenzene; D007501:Iron