Genotoxicity of pancreatic chemical carcinogens to propagable cultured normal pancreatic epithelial cells.
The cytotoxic and DNA-damaging effects of the pancreatic carcinogens azaserine, streptozotocin, and N-nitrosobis(2-oxyopropyl)amine (BOP) on propagable cultured normal rat pancreatic epithelial cells have been studied. All three chemicals in micromolar concentrations produced cytotoxicity to these cells. The concentrations that caused 50% reduction in colony formation (LD50) were approximately 0.3 mM for azaserine, 0.4 mM for BOP, and 2 mM for streptozotocin. Comparatively, the LD50 for N-methyl-N'-nitro-N-nitrosoguanidine was 3 microM. The toxicity of both azaserine and BOP did not require exogenously added S9 microsomal enzymes, indicating that the cells were capable of metabolic activation of these carcinogens. All three compounds induced unscheduled DNA synthesis, thus suggesting their mutagenic and carcinogenic potential in these cultured cells.
Shepherd
J
J
Department of Pathology, Montreal General Hospital, Quebec, Canada.
Tsao
M S
MS
Duguid
W P
WP
D000818:Animals; D001377:Azaserine / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D004247:DNA / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009602:Nitrosamines / Q000633:toxicity; D010179:Pancreas / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013311:Streptozocin / Q000633:toxicity
D002273:Carcinogens; D009602:Nitrosamines; D008769:Methylnitronitrosoguanidine; D013311:Streptozocin; C013622:nitrosobis(2-oxopropyl)amine; D001377:Azaserine; D004247:DNA