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 singlestrand breaks, in mice with different strain-dependent susceptibilityto 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 susceptibleto DMH-induced carcinogenesis. DNA breaks were estimated fromthe elution rate constant (K) according to the alkaline elutiontechnique. At 4 h after carcinogen administration a substantialand comparable DNA damage was found in liver and kidney in allthe strains examined. The DNA fragmentation index, however,reached a maximum value at 2 h after treatment in the liverof the most susceptible strain (SWR/J). About 50% of the liverDNA damage detected in all five strains 4 h after DMH administrationpersisted at 24 h after treatment and was totally repaired at72 h. Kidney DNA damage decreased in 48 h toward the range ofcontrol values. In colon epithelial cells (the carcinogen targettissue) 2 and 4 h after DMH administration the amount of DNAsingle strand breaks was correletable with the strain sensitivityto the carcinogen. In the time interval studied (2–72h after DMH administration) the decrease of colon DNA damagewas linear in the resistant strains. In contrast, in the moresusceptible strain (SWR/J), the amount of DNA breaks remainedhigh up to 24 h after treatment and returned to background levelat 72 h.