Susceptibility to Tumors Induced in Mice by Ethylnitrosourea Is Independent of Retinoblastoma Gene Dosage

Daniel J. Riley, Chen Ching Lai, Chi Yao Chang, Diane Jones, Eva Y.H.P. Lee, Wen Hwa Lee

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Abstract

The retinoblastoma gene (RB) is a classical tumor suppressor. Several studies have shown that RB dosage is important in determining biological effects. To explore the effect of RB dosage on susceptibility to cancer, three groups of congenic C57BL/6 mice, each of which expresses a different amount of Rb protein from one, two, or three alleles, were treated at postnatal day 12 with a single 60-mg/kg body weight i.p. dose of the DNA-alkylating agent N-ethyl-N’-nitrosourea (ENU). Mice heterozygous for the RB gene developed characteristic pituitary tumors with nearly complete penetrance, whether or not they were treated with ENU. Tumors initiated earlier or progressed more rapidly, however, in ENU-treated mice. Furthermore, although mice treated with ENU had a higher incidence of several nonpituitary tumors compared with untreated controls, no significant differences in the incidence of these tumors were found between wild-type mice (mRB+/+), mice carrying only one normal RB allele and deficient in Rb protein expression (mRB+/-), and mice overex-pressing Rb protein from two normal murine RB alleles and a human RB transgene (mRB+/+, hRB+/-). These studies underscore the tissue and mechanistic specificity of tumor predisposition caused by an inherited 50% reduction in RB dosage and indicate that most ENU-induced tumors occur independent of RB inactivation. Nonetheless, they suggest that certain point mutations induced by ENU may participate in the sequence of molecular steps involved in progression of tumor-prone, AR-deficient cells to the fully malignant state.

Original languageEnglish (US)
Pages (from-to)6097-6101
Number of pages5
JournalCancer Research
Volume54
Issue number23
StatePublished - Dec 1994

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Riley, D. J., Lai, C. C., Chang, C. Y., Jones, D., Lee, E. Y. H. P., & Lee, W. H. (1994). Susceptibility to Tumors Induced in Mice by Ethylnitrosourea Is Independent of Retinoblastoma Gene Dosage. Cancer Research, 54(23), 6097-6101.