Levels of myc, fos, Ha-ras, met and hepatocyte growth factor mRNA during regenerative cell proliferation in female mouse liver and male rat kidney after a cytotoxic dose of chloroform.
Chloroform is a liver carcinogen in mice and a kidney carcinogen in rats. It is thought to act through a non-genotoxic-cytotoxic mode of action. Changes in expression of growth control genes accompanying chloroform-induced cytolethality and regeneration may play a part in the development of chloroform-induced tumors. In this experiment, we examined the levels of the myc, fos, Ha-ras, met and hepatocyte growth factor mRNA in livers of female B6C3F(1) mice and kidneys of male F-344 rats to detect changes in gene expression following a single, cytotoxic gavage dose of chloroform in corn oil. Poly A+ RNA was purified from homogenates of livers of mice treated with 350mg/kg chloroform and kidneys of rats treated with 180 mg/kg chloroform and used for Northern blot analysis. Livers of female mice showed large transient increases in levels of myc and fos mRNA while levels of Ha-ras, met and the hepatocyte growth factor gene mRNA remained near control levels. In the male rat kidney, levels of myc mRNA increased after treatement, while levels of mRNA of all other genes examined remained near control levels. This pattern of gene expression is consistent with that induced by other cytotoxic carcinogens and suggest that alteration of the myc and fos genes could be involved in the regenerative cell proliferation that ultimately could play a role in chloroform-induced tumors.
Sprankle
C S
CS
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709-2137, USA.
Larson
J L
JL
Goldsworthy
S M
SM
Butterworth
B E
BE
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002725:Chloroform / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000032:analysis; D007668:Kidney / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D012737:Sex Factors; D013045:Species Specificity; D018631:ras Proteins / Q000032:analysis
D002273:Carcinogens; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D002725:Chloroform; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins