Genotoxicity potential of 8-Cl-cyclic adenosine monophosphate assessed with cytogenetic tests in vivo.
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.
Bajic
Vladan
V
GALENIKA a.d., Belgrade, Serbia and Montenegro. bladapfd@ptt.yu
Stanimirovic
Zoran
Z
Stevanovic
Jevrosima
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001835:Body Weight; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology; D004249:DNA Damage; D004912:Erythrocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D009153:Mutagens
D000970:Antineoplastic Agents; D009153:Mutagens; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003520:Cyclophosphamide