DNA damage, repair, replication, and tumor incidence in the BDIV rat strain following administration of N-ethyl-N-nitrosourea.
Berlin-Druckrey (BD-IV) rats were used to evaluate the level of neoplastic transformation, initiation of DNA damage and repair following treatment with N-ethyl-N-nitrosourea (ENU). ENU, a potent neurocarcinogen in the Sprague-Dawley (CD) and BDIX rat strains, was a less potent neurocarcinogen when administered to 30 day old BDIV rats. ENU induced significantly higher levels of tumors of the nervous system, kidney, and liver in CD rats than in BDIV rats. Initial DNA damage was determined by quantitating and comparing the number of alkaline labile sites (ALS) and alkylation of [14C]ENU to deoxyguanosine in the brain, kidney, and liver of BDIV rats. A smaller percentage of ALS were lost from the DNA of the brain (10-15%) than from the kidney (19-27%) and liver (30%). Similarly, loss of 0(6)-ethylguanine was greatest in liver (100%), next in kidney (73%), and least in brain (23%) DNA during a seven-day period. Loss of N7-ethylguanine ranged between 23-44%. These levels of repair are similar to those previously observed in the more sensitive Sprague-Dawley rat. Cellular replication was highest in the liver and lowest in the brain of BDIV rats at 30 days of age and was inhibited to varying extents in all three tissues by ENU. These data indicate, that while there is a good correlation between organ sensitivity to ENU induced carcinogenesis and the persistence of DNA lesions and levels of DNA replication in the same strain of rat, there is no correlation across strains with different carcinogenic potential.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004260:DNA Repair; D004261:DNA Replication; D005038:Ethylnitrosourea; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D005038:Ethylnitrosourea