Evaluation of streptozotocin genotoxicity in rats from different ages using the micronucleus assay.
Genotoxic potential of streptozotocin (STZ), a naturally occurring antibiotic, has been reported in rat by employing micronucleus (MN) test as the end of evaluation. Influence of age (neonatal, young and adult) was studied for the induction of genotoxicity in peripheral blood and bone marrow. Studies with 3 different doses (10, 30 and 100mg/kg) and three different time periods (1, 3 and 7 days) were conducted to induce MN in peripheral blood reticulocytes (RETs) and bone marrow polychromatic erythrocytes (PCEs). Bone marrow and peripheral blood were analyzed after 24h of last treatment. The induction of MN was observed in both neonatal and young rat peripheral blood RETs as well as in bone marrow PCEs. Results demonstrate the genotoxic nature of STZ in a dose dependent manner. However, significant induction of MN was observed only in bone marrow PCEs of adult rats. The genotoxic potential of STZ (30 mg/kg x 3 days) was further evaluated using comet assay in both bone marrow cells and peripheral blood lymphocytes of young rats. It was found that STZ induced significant DNA damage in comet assay as well. Our data indicate the suitability of neonatal and young rat over adult rats for peripheral blood MN assay. In conclusion, both MN and comet assay can be used as suitable end-points for genotoxic risk assessment in a regulatory set-ups. This can add further advantage of integrating genotoxicity assessment in routine toxicological studies using young rat as a model.
Vikram
A
A
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India.
Tripathi
D N
DN
Ramarao
P
P
Jena
G B
GB
D000367:Age Factors; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000097:blood; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests / Q000379:methods*; D009152:Mutagenicity Tests / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D008054:Lipid Peroxides; D013311:Streptozocin