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Chromosome aberrations induced by clinical medicines
The Journal of Toxicological Sciences
|May 1, 1980
Summary
Eleven common internal medicines were tested for their ability to induce chromosome aberrations in mammalian cells. Several drugs, including isonicotinic acid hydrazid and streptomycin A, significantly increased aberrations, necessitating further safety evaluations.
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Long-term use of clinical medicines in internal medicine necessitates evaluation of their potential genotoxicity.
- Assessing the inducibility of chromosome aberrations is crucial for understanding drug safety profiles.
Purpose of the Study:
- To investigate the chromosome aberration-inducing potential of 11 commonly used clinical medicines.
- To compare the effective concentrations in vitro with clinical blood concentrations to assess in vivo risk.
Main Methods:
- Cultured mammalian cells were exposed to 11 different clinical medicines.
- Chromosome aberration frequencies were quantified and analyzed.
- In vitro effective concentrations were compared to reported human maximum blood concentrations.
Main Results:
- Isonicotinic acid hydrazid, streptomycin A, hydralazine hydrochloride, methimazole, and theophylline demonstrated a definite increase in chromosome aberrations.
- P-aminosalicilic acid showed a weaker effect, while rifamycin SV, aminophylline, and isosorbide dinitrate had suspicious effects (slight increases).
- Reserpine and propylthiouracil induced minimal chromosome aberrations.
Conclusions:
- Several commonly used internal medicines exhibit genotoxic potential by inducing chromosome aberrations.
- High ratios of effective to clinical concentrations for some drugs suggest potential in vivo risk.
- Further safety evaluations are recommended for p-aminosalicilic acid, rifamycin SV, hydralazine hydrochloride, and aminophylline due to positive or suspicious findings.