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

Sprankle, Catherine S.; Larson, Jeffrey; Goldsworthy, Susan M.; Butterworth, Byron E.

doi:10.1016/0304-3835(96)04123-7

Cited by 8 publications

(1 citation statement)

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“…Increased cell turnover can increase the rate of conversion of DNA adducts from endogenous and exogenous sources to mutations before DNA repair can occur. In addition, many genes responsible for growth control are also oncogenes and may exhibit increased expression in regenerating tissue [11][12][13][14]. Alteration in the sequence or expression of such genes can be involved in carcinogenesis [15,16].…”

Section: Introductionmentioning

confidence: 99%

Differential display identified changes in mRNA levels in regenerating livers from chloroform-treated mice

et al. 1997

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The nongenotoxic-cytotoxic carcinogen chloroform induces liver necrosis, regenerative cell proliferation, and, eventually, liver tumors in female B6C3F1 mice when administered by gavage at doses of 238 or 477 mg/kg/d. Administration of 1800 ppm of chloroform in the drinking water results in similar daily doses but does not produce liver toxicity or cancer. The differential-display technique was used to compare the expression of a subset of mRNAs in normal (control) and regenerating liver after chloroform-induced toxicity to define the proportion of genes whose expression changes under hepatotoxic conditions and to identify the genes that might play a role in regeneration and perhaps cancer. RNA was purified from the livers of female B6C3F1 mice after 4 d or 3 wk of gavage treatment with 3, 238, or 477 mg/kg/d of chloroform or treatment with 1800 ppm chloroform in drinking water. There was a remarkably high degree of consistency of gene expression among the animals and across dose and treatment groups as visualized by the differential-display technique. Of the 387 bands observed, only four (about 1%) changed expression in regenerating liver. The genes were assigned locus names by GenBank after sequence submission. The genes with increased mRNA levels as confirmed by northern blot analysis were MUSTIS21, a mouse primary response gene induced by growth factors and tumor promoters; MUSMRNAH, a gene highly homologous to a human gene isolated from a prostate carcinoma cell line; and MUSFRA, a novel gene. The novel gene MUSFRB exhibited decreased mRNA levels. No change in expression was seen among control mice given the nontoxic regimens of 3 mg/kg/d chloroform or 1800 ppm chloroform in drinking water, indicating that changes in expression were associated with toxicity and regeneration rather than chloroform per se. These genes and others that may be identified by expanding this approach may play a role in regeneration and perhaps in the process of chloroform-induced carcinogenesis in rodent liver.

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