The effect of the mode of administration of nitrogen mustard and cytosine arabinoside on the production of chromosomal aberrations in mouse bone marrow and ascites tumour cells

Abstract

The cytogenetic effects of intraperitoneally (i.p.) and subcutaneously (s.c.) administered nitrogen mustard (HN2) and cytosine arabinoside (ara-C) on bone-marrow and ascites tumour cells of mice were studied. Ehrlich ascites tumour-bearing mice were treated with the mutagens, and cytological preparations were made from ascites tumour and bone-marrow cells of the same animal. The following parameters were investigated: frequencies of mitotic and chromosomal aberrations, time of aberration maxima and aberration spectra. HN2 (0.68 mg/kg b.w.), when given i.p., induced in ascites tumour cells a strong inhibition of mitotic frequency and very high aberration rates, whereas in bone marrow no aberrant chromosomes were observed. On the other hand, after s.c. administration, the same dose induced more aberrant metaphases in bone marrow than in tumour cells. Ara-C (315 mg/kg b.w.) resulted, after s.c. administration, in higher aberration frequencies both in ascites and bone-marrow cells compared with i.p. treatment. All ascites tumour cells showed higher aberration frequencies than bone-marrow cells. In bone marrow the aberration maximum occurred as soon as 6 h after treatment. Furthermore, clear differences with respect to the types of aberration found in the two systems were evident. The differences caused by the different modes of administration in two different types of cell are discussed in terms of metabolic inactivation and differences of the two tissues with respect to karyotype, cell cycle time and repair capacity.