Persistence of drug-induced chromosome aberrations in peripheral blood lymphocytes of the rat.
We have studied the persistence of pre-clastogenic lesions, detected as induced chromosomal aberrations, in rat peripheral lymphocytes at various time intervals after acute treatment with 3 different antineoplastic drugs: cyclophosphamide (CPA), 5-fluorouracil (5-FU) and adriamycin (AM). Single i.p. doses were administered to groups of rats and heart blood samples from each group were taken after 3, 12, 24 or 48 h or weekly up to 20 weeks later. The cytogenetic analysis was performed on lymphocytes cultured for 33 h after sampling. The results for CPA exposure (10 mg/kg) show that the yield of chromosome aberrations is maximal 3 h after the treatment (20 times the control level). For up to 8 weeks the values remain about 6 times the baseline; afterwards a decrease is observed and the control level is reached after 20 weeks. For 5-FU (50 mg/kg) a remarkable increase (13-fold) in chromosomal damage is observed at the first sampling time. Within 48 h the effect is drastically reduced but persistent (3 times the control level), and the level returns to spontaneous values 1 week later. AM treatment (2 mg/kg) induced an increase of about 8 times the control level at 3 h post exposure. The clastogenic effects remained at a detectable level for 1 week (about 6 times the control level at all sampling times); 2 weeks after the treatment the control level was found. A parallel analysis was performed on bone marrow cells. In this tissue the clastogenic effects of the treatments were maximal, as in lymphocytes, at the first sampling time (20-25 times the control level) and were no longer detectable within 72 h after exposure, irrespective of the administered drug.
Rosselli
F
F
Dipartimento di Scienze dell'Ambiente e del Territorio, Universitá degli Studi di Pisa, Italy.
Zaccaro
L
L
Venturi
M
M
Rossi
A M
AM
D000818:Animals; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D009153:Mutagens / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009153:Mutagens; D004317:Doxorubicin; D003520:Cyclophosphamide; D004247:DNA; D005472:Fluorouracil