Genotoxic effect of Anovlar 21, an oral contraceptive, on mouse bone marrow.
Anovlar 21, a combination drug containing the oestrogen ethinyloestradiol and the progestin norethisterone acetate, was studied for its in vivo genotoxic effect on the bone marrow cells of Swiss albino mice. The chromosomal aberration assay and the micronucleus test were employed for the study. 0.08, 0.4, 0.8, 1.6, 3.2, 4.8, 6.4 and 8.0 mg/kg/day of the drug was orally administered for 15 consecutive days to mice. Bone marrow preparations were made 24 h after the final feeding. The lowest dose, 0.08 mg/kg, represents the human therapeutic range. Marrow preparations of mice fed 0.8 mg/kg/day for 15 days were made at 6, 12, 24, 48 and 96 h, and 1, 2 and 3 weeks and a time-yield analysis was carried out. Statistically significant increases in chromosomal aberrations were observed in animal groups fed doses of greater than or equal to 0.4 mg/kg/day. In the time-response study, the maximum frequency of aberrations was noted at 24 h, thereafter decreasing gradually with increasing time. But the drug did not induce a significant increase in the number of micronuclei in bone marrow erythrocytes at any of the doses or time intervals studied.
Shyama
S K
SK
Department of Biosciences, Mangalore University, Mangalagangotri, India.
Abdul Rahiman
M
M
Vijayalaxmi
K K
KK
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology* / Q000633:toxicity; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009640:Norethindrone / Q000633:toxicity*; D013997:Time Factors
D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C020416:norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination; D004997:Ethinyl Estradiol; D004247:DNA; D009640:Norethindrone