Abstract
Female Sprague-Dawley rats bearing methylnitrosourea-induced mammary carcinomas were treated with 100 mumol 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU)/kg to investigate the time course of DNA-DNA interstrand cross-linking (DNA-XL) as measured by alkaline elution in tumor, bone marrow and liver cells. The inhibition of bone marrow stem cell colony formation in culture (CFU-C) and in spleens of lethally irradiated mice (CFU-S), serum transaminase levels and total bilirubin were concomitantly determined. All parameters were evaluated at different times from 4 to 72 h after treatment. The highest amounts of DNA-XL were found in tumor cells, peaking at 24 h after treatment. A parallel increase was observed in bone marrow cells up to 16 h with a subsequent rapid decrease to about one-third of DNA-XL in tumor cells after 72 h. Concomitantly, CFU-C and CFU-S were suppressed, the nadir being at 24 h after treatment. In liver cells, however, constant low levels of DNA-XL were found, which had disappeared after 48 h. In accordance with this observation, serum transaminase levels were only slightly elevated.