Storage enhances chromosome damage after exposure of human leukocytes to mitomycin C

Abstract

Two of the distinctive differences between the mutagenic repsonse of Drosophila sperm exposed to X rays and to alkylating agents, are: (1) an increase in the incidence of chromosomal structural changes with increasing storage time (days, or weeks) prior to fertilisation following treatments with chemical mutagens, but not X rays, and (2) the frequent occurrence of F₁ individuals mosaic for either mutation or chromosome structural change after chemical treatment, but not after X-ray radiation¹. Similar time-dependent increases in mutations and chromosome aberrations have also been reported for fungal spores² and plant seed root meristem cells³ exposed to alkylating agents, but no enhancing effect of storage could be demonstrated in confluent human fibroblasts exposed to an alkylating agent in vitro⁴. We show here that a storage effect can be demonstrated for sister chromatid exchange (SCE) and, to a much greater extent, for chromosome structural changes in human lymphocytes exposed to mitomycin C and stored for various periods before stimulation with phytohaemagglutinin (PHA). Moreover, mitomycin C-treated G₀ cells, which normally develop only chromatid-type aberrations, also yield chromosome-type changes after storage. This result implies a time-dependent alteration in the induced lesions following storage, and predicts a decreasing incidence of mosaicism with increasing storage time—a result that has indeed previously been reported for stored Drosophila sperm⁵.