Induction of micronucleated erythrocytes in mouse peripheral blood after cutaneous application of 5-fluorouracil

Arch Med Res. 2003 Mar-Apr;34(2):141-4. doi: 10.1016/S0188-4409(02)00470-8.

Abstract

Background: For topically applied drugs such as 5-fluorouracil (5-FU), dosage is not as precise as for other drug administration pathways. Consequently, quantity of drug delivered may differ among individuals and applications. 5-FU is used in treatment of different diseases and has been reported as a clastogenic compound by micronucleus assay.

Methods: To determine whether 5-FU cream (5% 5-FU) absorbed through skin can produce genotoxic or cytotoxic effect in mouse bone marrow, induction of micronucleated erythrocytes (MNE) in mouse peripheral blood was examined after cutaneous application of 5-FU daily for 5 days.

Results: 5-FU cream induced significant micronuclei at doses of 37.5 mg (total weight of cream)/2 cm(2) and 75.0 mg/2 cm(2), as well as cytotoxic effects at doses of 150.0 and 300.0 mg/2 cm(2).

Conclusions: Cutaneous application of 5-FU increased number of MNE in mouse peripheral blood. These data emphasize the importance of using correct dose when applying drugs topically.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology
  • Erythrocytes / metabolism*
  • Fluorouracil / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Micronuclei, Chromosome-Defective / drug effects*
  • Micronuclei, Chromosome-Defective / metabolism*
  • Micronucleus Tests
  • Time Factors

Substances

  • Antimetabolites, Antineoplastic
  • Fluorouracil