Genotoxicity potential of 8-Cl-cyclic adenosine monophosphate assessed with cytogenetic tests in vivo.

摘要

BACKGROUND: Growth-modulating noncytotoxic activity of 8-chloro-adenosine 3',5'-cyclic monophosphate (8-Cl-cAMP) showed inhibitory effect on growth of a wide variety of cancer cell lines in vitro and in vivo. To assess possible genotoxic effects of 8-Cl-cAMP, we conducted a study in vivo using male BALB/c mice. METHODS: Clastogenic effects were estimated by bone marrow micronucleus assay and cytogenetic test in adult mice BALB/c strain. 8-Cl-cAMP was administered intraperitoneally (i.p.) to three dose groups including 10 mg/kg body weight (b.w.), 90 mg/kg b.w., and 160 mg/kg b.w., with saline solution as negative control and cyclophosphamide, a known mutagen, and clastogen as positive control during a 7-day period in 24-h intervals. RESULTS: Micronucleus test in vivo results showed consistently increasing dose-dependent pattern increase of dose regime (10 mg/kg body weight [b.w.], 90 mg/kg b.w., and 160 mg/kg b.w.), and increase in frequency of micronuclei in polychromatic erythrocytes (4.88 +/- 0.35, 8.32 +/- 0.57, and 11.74 +/- 0.37) compared to negative control (2.04 +/- 0.28). Quantitative effects are paralleled by structural changes in chromosome morphology. 8-Cl-cAMP induced structural (breaks, gaps, centric rings, acentrics, and Robertsonian translocations) and numerical-type chromosomal aberrations (aneuploidy and polyploidy). CONCLUSIONS: Results of this study demonstrate that 8-Cl-cAMP has genotoxic potential in vivo.