The Action of Cytostatic Agents on the Chromosomes of Human Leukocytes in Vitro (Preliminary Communication)

Abstract

Quantitative analysis of the chromosomal injuries following in vitro addition of various cytostatic agents to short-term human leukocyte cultures was carried out. The data obtained suggest that the cytogenic action of these various compounds in vitro follows a pattern similar to its action when administered therapeutically to man. The technics used may form the basis of further evaluation of the cytogenetic activity of these various compounds.

Effect of azathioprine on the chromosome complement of human bone marrow cells

“…A similar discrepancy exists between the results of various cytogenetic studies dealing with other chemical agents, viz. the folic acid antagonists (Ryan et al, 1965;Hampel et al, 1966;Krogh Jensen, 1967) and lysergic acid diethylamide (Cohen et al, 1967;Irwin and Egozcue, 1967;Loughman et al, 1967;Bender and Sankar, 1968;Nielsen et al, 1968) and some viruses, viz. morbilli (Nichols et al, 1962;Tanzer et al, 1963;Aula, 1965;Gripenberg, 1965), and rubella viruses (Mellman et al, 1965;Nusbacher et al, 1967).…”

Chromosome abnormalities from cyclophosphamide therapy in rheumatoid arthritis and progressive systemic sclerosis (scleroderma)

“…This alkylating agent has been shown to combine and crosslink DNA strands (4); thus prolonged therapy may alter the structural integrity of chromosomes. Cytogenetic studies in animals indicate that large doses of cyclophosphamide cause aberrations similar to those observed with x-irradiation (5)(6)(7). However, there are only preliminary and inconclusive clinical reports which evaluate the frequency of cytogenetic aberrations in man (8)(9)(10)(11).…”

Human mitotic and meiotic chromosome damage following in vivo exposure to methotrexate

“…Recent contradictory reports on the effects of LSD have focused attention on the possible teratogenic and cytogenetic damage of this and other drugs in humans. Methotrcxatc (amcthopterin), which is being widely used in the treatment of psoriasis, has been reported to induce mitotic chromosome breakage in some studies (Jensen 1967, Kuang & Swartzendruber 1969, Locher & Franz 1967.5) but not in others (Hampel et al 1966, Voorhees et al 1969. To further evaluate the effects of this drug, we have simultaiieously evaluated four different tissues in one patient.…”