Comparison of genomic damage caused by 5-nitrofurantoin in young and adult mice using the in vivo micronucleus assay.
The antibiotic 5-nitrofurantoin (5-NF) has been used widely for the treatment of urosepsis in children during the last 20 years. Recent experimentation suggests the need for reevaluating its genotoxic potential. Because of possible differences in the metabolism and clearance of 5-NF in young and adult animals, we conducted a study to determine whether micronuclei caused by 5-NF were age-related. The in vivo micronucleus (MN) assay was performed on 3- and 8-week-old mice given single intraperitoneal injections of 5, 10, and 50 mg/kg 5-NF. Blood samples from the tail vein were taken before injection (baseline) and at 48, 96, 168, and 336 hr (2 weeks) after the treatment. One thousand reticulocytes were analyzed for micronuclei from each animal. Compared to similar baseline values for young and adult mice, 5-NF caused a significant increase in MN frequency in both age groups. The mean MN frequency in the young animals was higher than in the adult animals for each dose and sampling time. MN frequencies remained significantly elevated in young animals even 2 weeks after exposure to 5-NF. The results of the study confirm the genotoxic potential of 5-NF in young and adult animals, and indicate that young animals are more sensitive to the genotoxic effects of 5-NF than adult mice and that the response in young mice persists for a significantly longer time. These findings may be related to poorly developed mechanisms of xenobiotic detoxification and renal elimination in young animals.
Fucić
Aleksandra
A
Institute for Medical Research and Occupational Health, 10000 Zagreb, Ksaverska c2, Croatia. afucic@imi.hr
Marković
Darko
D
Ferencić
Zeljko
Z
Mildner
Boris
B
Jazbec
Ana-Marija
AM
Spoljar
Jadranka Bubić
JB
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D008658:Inactivation, Metabolic; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009582:Nitrofurantoin / Q000009:adverse effects* / Q000493:pharmacokinetics; D012156:Reticulocytes / Q000187:drug effects; D013997:Time Factors
D000892:Anti-Infective Agents, Urinary; D009582:Nitrofurantoin