Abstract

5-fluorouracil (5-FU) is an analogue of uracil that is widely used in the treatment of a variety of cancers such as breast, ovarian, uterine and colon cancers. However, it has a narrow margin of safety and is a highly toxic drug. It causes serious side effects such as myleosupression and its clastogenic potential has been reported in many studies. Several reports have suggested that dietary supplementation with antioxidants can influence the undesired side effects that result from treatment with anticancer agents. Chlorophyllin (CHL) is an antioxidant that has been reported to protect against clastogenesis in vivo and in vitro assays. The aim of the current study was to evaluate the ability of CHL to protect against the clastogenic action of the anticancer drug 5-FU in mice bone marrow cells. The mice were injected i.p. with CHL (2, 4 and 6 mg/kg BW) 24 h before i.p. administration of 5-FU (10 mg/kg BW) and then sacrificed 24 h after treatment. The clastogenic potential of 5-FU was determined by chromosomal aberrations (CAs) and micronucleus (MN) assays. To evaluate the possible modification of the antitumor activity of 5-FU by CHL, we studied their interaction in Ehrlich ascites carcinoma (EAC) bearing mice. The results of the present study revealed that CHL pretreatment at the three tested dose levels caused a significant decrease in the total number of cells with CAs and in the number of polychromatic erythrocytes (PCEs) with MN in a dose-dependent manner. Despite the reduction of 5-FU clastogenicity by CHL, the results revealed that CHL reduced also the antitumor activity of 5-FU.

Key words: Chlorophyllin, 5-fluorouracil, Clastogenicity, Chromosomal aberrations, Micronucleus assay