133 Mutation Research, 79 (1980) 133--140 © Elsevier/North-Holland Biomedical Press IN VIVO DOSE--RESPONSE RELATIONSHIP IN BONE-MARROW CELLS OF MICE TREATED WITH ADRIAMYCIN M.L. LARRAMENDY, F.N. DULOUT, N.O. BIANCHI and O.A. OLIVERO Instituto Multidisciplinario de Biologia Celular (IMBICE), La Plata (Argentina) (Received 22 January 1980) (Accepted 21 April 1980) Summary In bone-marrow cells of mice treated with a single dose of adriamycin and killed 6 h later, only chromatid-type aberrations were found. Animals studied 12 h after adriamycin injection showed chromatid- and chromosome-type aber- rations, including Robertsonian centric fusions. The frequency of chromatid- type aberrations exhibited a direct correlation with the dose in mice treated for 6 but not for 12 h. On the other hand, chromosome-type aberrations detected 12 h after injection were directly correlated with the dose of adriamycin. The induction in vivo of chromosome-type aberrations in mice studied 12 h after treatment suggests the existence of bone-marrow cell populations able to carry out 2 mitoses in this time lapse. The induction of Robertsonian fusions can be explained by the preferential induction of chromosomal lesions in pericentro- meric heterochromatin followed by reunion of damaged segments of 2 chromo- somes. Consequently, the metacentric-like chromosomes induced by adriamy- cin arise either from translocations involving entire chromosome arms or from aberrations of the exchange type between 2 short arms of acrocentric chromo- somes. The antibiotic adriamycin (14-hydroxydaunomycin) is an antileukaemic antitumour agent, which belongs to the group of anthracyclines. The main genetic effect of this and related compounds is the binding to DNA and, conse- quently, the interference with template DNA function (Di Marco and Arca- mone, 1975). The genetic toxicology of anthracycline antibiotics has been reviewed by Vig (1977). These antibiotics cause aberrations of chromosome as well as chro- matid type, and this effect has been extensively analysed in lymphocytes from patients under therapeutic treatment, in lymphocyte cultures from healthy donors and in cultures of various cell lines (Hsu et al., 1975; Kusyk and Hsu, 1976; Newsome and Littlefield, 1975; Vig, 1971, 1977).