Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: comparison of the in vivo and in vitro assays.
The capability of covalent binding to DNA to predict the initiating potential of chemical carcinogens was compared for the assays performed in vivo (rodent liver DNA) and in vitro (purified DNA incubated in the presence of mouse and rat liver microsomes). A quantitative correlation between DNA adducts and carcinogenic potency was investigated. The in vivo assay appeared slightly, but not significantly, more predictive than the in vitro assay. Also predictivity was slightly higher both in vivo and in vitro when we referred to liver carcinogenicity instead of overall carcinogenicity. The predictive ability found for DNA covalent binding (both in vivo and in vitro) was similar to that of many short-term tests (such as mutagenicity, DNA damage/repair, SCEs, and cell transformation tests). The covalent DNA binding, measured after incubation with DNA in vitro in the presence of liver microsomes, could therefore be a reasonable short-term test offering greater rapidity of execution and requiring the sacrifice of fewer animals than the corresponding in vivo test.
Taningher
M
M
Centro Interuniversitario per la Ricerca sul Cancro, Università di Genova, Italy.
Saccomanno
G
G
Santi
L
L
Grilli
S
S
Parodi
S
S
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011237:Predictive Value of Tests; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects
D002273:Carcinogens; D004247:DNA