Differential capacities for DNA repair in Clara cells, alveolar type II cells and macrophages of rabbit lung.
The ability to repair damaged DNA was determined in different cell populations of rabbit lung cells isolated by centrifugal elutriation. DNA excision repair, measured as unscheduled DNA synthesis, was examined in in vitro confluent primary cultures. A dose dependent level of DNA excision repair was observed in alveolar type II cells after exposure to the direct acting alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N-nitrosourea and methyl methansesulphonate. Furthermore, O6-alkylguanine-DNA alkyltransferase activity was easily detectable in alveolar type II cells and alveolar macrophages. In contrast, non-ciliated (Clara) cells had 4 to 20-fold lower levels of DNA excision repair and non-detectable levels of O6-alkylguanine-DNA alkyltransferase. Uracil-DNA glycosylase activities in Clara cells and alveolar type II cells were in the same range and had 3-fold lower activity than alveolar macrophages. Our findings indicate that various lung cells differ in DNA repair capacity and may thus differ in sensitivity to some carcinogens.
D000818:Animals; D002273:Carcinogens / Q000502:physiology*; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects; D005038:Ethylnitrosourea / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011817:Rabbits
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea