Inhibition of Methotrexate-Induced Chromosomal Damage by Folinic Acid in V79 Cells

Details

• Personal Author:
  Keshava C ; Keshava N ; Nath J ; Ong TM ; Whong, Wen-Zong
• Description:
  Methotrexate (MTX), an anticancer compound, is widely used in the treatment of leukemia. It induces cytogenetic damage as well as cytostatic effects on a variety of cell systems. Folinic acid (Leucovorin) is generally administered along with MTX as a rescue agent to decrease MTX-induced toxicity. However, information regarding the inhibitory effect of folinic acid against cytogenetic damage caused by MTX is limited. This study was conducted to assess the cytogenetic effect of MTX and its inhibition by folinic acid (FA) using the micronucleus and chromosomal aberration assays concurrently. Exponentially growing V79 cells were treated with MTX at five different concentrations (5-100 micrograms ml-1) with S9 microsomal fraction for 6 h and post-treated with two concentrations of FA (5 or 50 micrograms) for 40 h. Results indicate that MTX alone induced a concentration-related increase in % micronucleated binucleated cells (MNBN) and % aberrant cells (Abs). There was a decrease in nuclear division index (NDI) with increase in MTX concentration. Similarly, the mitotic index (MI) also decreased in all concentrations of MTX tested. The addition of FA at 50 micrograms ml-1 significantly reduced % MNBN (40-68%) and % Abs (36-77%). Inhibition was also seen at 5 micrograms FA (12 to 54% for MNBN and 20 to 61% for Abs). These results indicate that FA is capable of reducing the cytogenetic damage induced by MTX and appears to be an anticlastogenic agent. [Description provided by NIOSH]
• Subjects:
  Chromosomes Hazardous Substances Neoplasms Occupational Health Safety
• Keywords:
  Anticancer Drug Author Keywords: Methotrexate Cancer Cell-transformation Cellular-function Cellular-reactions Cellular-structures Cellular-uptake Chromosomal Aberration Chromosome-damage Chromosome-disorders Dihydrofolate Reductase Folinic Acid (leucovorin) In-vitro-studies In-vivo-studies Micronucleus Toxic-effects Toxins V79 Cell

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• ISSN:
  0027-5107
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  221-228
• Volume:
  397
• Issue:
  2
• NIOSHTIC Number:
  nn:20025170
• Citation:
  Mutat Res 1998 Feb; 397(2):221-228
• CAS Registry Number:
  Methotrexate (CAS RN 59-05-2)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  True
• Source Full Name:
  Mutation Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:69fdf8eebead819750ab9249bd099d1531a86f397fb880b2ab9f1e9eeffbacd3fb3d5ff9b558123f012bcbcc3db4daf0f001890bc67b6bc04f600fc84e13468d
• Download URL:
  https://stacks.cdc.gov/view/cdc/196653/cdc_196653_DS1.pdf
• File Type:
  [PDF - 220.79 KB ]