Target tissue DNA damage in inbred mouse strains with different susceptibility to the colon carcinogen 1,2-dimethylhydrazine.

We have compared liver, kidney and colon DNA damage, as single strand breaks, in mice with different strain-dependent susceptibility to the colon-specific carcinogen 1,2-dimethylhydrazine (DMH). The mouse strains studied were: AKR/J, DBA2 totally resistant; CD1, C57BL/6N moderately susceptible; SWR/J very susceptible to DMH-induced carcinogenesis. DNA breaks were estimated from the elution rate constant (K) according to the alkaline elution technique. At 4 h after carcinogen administration a substantial and comparable DNA damage was found in liver and kidney in all the strains examined. The DNA fragmentation index, however, reached a maximum value at 2 h after treatment in the liver of the most susceptible strain (SWR/J). About 50% of the liver DNA damage detected in all five strains 4 h after DMH administration persisted at 24 h after treatment and was totally repaired at 72 h. Kidney DNA damage decreased in 48 h toward the range of control values. In colon epithelial cells (the carcinogen target tissue) 2 and 4 h after DMH administration the amount of DNA single strand breaks was correlatable with the strain sensitivity to the carcinogen. In the time interval studied (2-72 h after DMH administration) the decrease of colon DNA damage was linear in the resistant strains. In contrast, in the more susceptible strain (SWR/J), the amount of DNA breaks remained high up to 24 h after treatment and returned to background level at 72 h.