In vivo effects of cyclophosphamide on oncogene and suppressor gene expression in a "follow up" study

Anticancer Res. 1997 Sep-Oct;17(5A):3593-7.

Abstract

Cyclophosphamide is a chemotherapeutical drug, with proved carcinogenic side effects. Our previous experiments showed its effect on the expression of certain oncogenes and tumor suppressor genes. In order to further explore the effects of cyclophosphamide at the gene level an in vivo mouse model was developed. We compared the effects of cyclophosphamide with that of cyclosporine, which is a non genotoxic human carcinogenic chemical. After different time periods of intraperitoneal cyclophosphamide or cyclosporine injection, RNA was isolated from whole organs of experimental animals, and expression of onco/suppressor genes was determined by slot blot hybridisation. In our model we have proved that gene expression changes caused by cyclophosphamide can be detected even six months after treatment without tumor development. Our results support the hypothesis that gene expression investigations could be useful biomarkers in monitoring the effects of environmental carcinogenic compounds.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Carcinogens / pharmacology*
  • Cyclophosphamide / pharmacology*
  • Cyclosporine / pharmacology
  • Female
  • Gene Expression / drug effects
  • Genes, myc*
  • Genes, p53*
  • Genes, ras*
  • Male
  • Mice
  • Mice, Inbred CBA
  • Oncogenes*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA, Messenger / genetics
  • Spleen / physiology
  • Thymus Gland / physiology
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents, Alkylating
  • Carcinogens
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Cyclosporine
  • Cyclophosphamide
  • Proto-Oncogene Proteins p21(ras)