The genotoxicity of DNA intercalating drug 8-methoxy pyrimido [4',5':4,5]thieno(2,3-b)quinoline-4(3H)-one.
8-methoxypyrimido[4',5':4,5]thieno(2,3-b)quinoline-4(3H)-one (MPTQ) is known to have antitumor and cytotoxic activities on various types of tumors. This compound showed a strong clastogenic effect on bone marrow cells of Swiss albino mice treated in vivo (17.5-35 mg/kg body weight). MPTQ induced micronuclei formation (MN) at doses of 17.5, 23.3, and 35 mg/kg. Dose and time-yield effect of MPTQ was studied in the case of chromosome aberration assay. MPTQ induced a statistically significant increase in the frequency of chromosome aberrations and micronuclei induction. The drug induced significant abnormal sperms even in the sperm shape abnormality assay. Based on the data reported in the literature, we have tried to establish the relationship between the clastogenic effect observed and process of MPTQ intercalation into DNA and the formation of protein-associated DNA-strand breaks probably promoted by topoisomerase enzymes.
Shahabuddin
M S
MS
Department of Studies in Biochemistry, Kuvempu University, Shivagangotri, Davanagere, India.
Gopal
M
M
Vijayalaxmi
K K
KK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000648:ultrastructure; D002869:Chromosome Aberrations / Q000139:chemically induced; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D007364:Intercalating Agents / Q000633:toxicity*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens; D009929:Organ Size / Q000187:drug effects; D011804:Quinolines / Q000633:toxicity*; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure; D013876:Thiophenes / Q000633:toxicity*
C488380:8-methoxypyrimido(4(1),5(1)-4,5)thieno(2,3-b)quinoline-4(3H)-one; D007364:Intercalating Agents; D009153:Mutagens; D011804:Quinolines; D013876:Thiophenes; D004247:DNA