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Study of a rat skin in vivo micronucleus test: data generated by mitomycin C and methyl methanesulfonate

T Nishikawa1, M Haresaku, K Adachi

  • 1Human Safety Evaluation Center, Lion, 100 Tajima, Odawara-shi, Kanagawa 256-0811, Japan. ntaka@lion.co.jp

Mutation Research
|September 8, 1999
PubMed

Insights

This study introduces a new in vivo micronucleus (MN) test using rat skin. The assay effectively detects genotoxic effects of chemicals like mitomycin C (MMC) and methyl methanesulfonate (MMS) in skin cells.

Area of Science:

  • Toxicology
  • Genetics
  • Dermatology

Background:

  • The micronucleus (MN) test is a standard assay for detecting genotoxicity.
  • Existing MN tests often target internal organs, necessitating invasive procedures.
  • A non-invasive or less invasive skin-based MN test could offer advantages in toxicological assessments.

Purpose of the Study:

  • To develop and validate a novel in vivo micronucleus (MN) test utilizing rat skin as the target organ.
  • To assess the sensitivity of the rat skin MN test to known clastogenic agents.

Main Methods:

  • Epidermal tissue was isolated from rats after cold trypsin treatment and forceps peeling.
  • Isolated epidermis was subjected to hypotonic treatment and stained with acridine orange (A.O.).
  • The assay was validated using mitomycin C (MMC) and methyl methanesulfonate (MMS) as model clastogens, with single and repeat dosing regimens.

Main Results:

  • Both MMC and MMS induced a significant, dose-dependent increase in the frequency of micronuclei in basal epidermal cells.
  • A repeat treatment regimen of one dose per day for three consecutive days was found to be optimal for MN induction.

Conclusions:

  • The developed rat skin in vivo micronucleus test is a sensitive and viable method for genotoxicity assessment.
  • This assay provides a valuable tool for evaluating the genotoxic potential of chemicals targeting the skin.

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