The influence of molecular size and partition coefficients on the predictability of tumor initiation in mouse skin from mutagenicity in Salmonella typhimurium.
Initiation of tumors in mouse skin is well correlated with mutagenesis in hamster V79 cells (correlation coefficient r = 0.88), but is poorly correlated with bacterial mutagenicity in the Ames assay (r = 0.58). Efforts to understand the difference in the degrees of correlation led to the observation that if the bacterial mutagenicity data are combined with a molecular size or partition factor, the correlation of initiating activity with this combined parameter approaches that found with the hamster cell mutagenesis. The improvement in correlation (r = 0.84) leads to the suggestion that when a broad size range of compounds is considered a most important factor in accounting for the poor correlation initially observed may be a difference between mammalian and bacterial cells in permeability or target access.
Scribner
N K
NK
Pacific Northwest Research Foundation, Seattle, WA 98104, USA.
Woodworth
B
B
Ford
G P
GP
Scribner
J D
JD
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D006224:Cricetinae; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005798:Genes, Bacterial / Q000187:drug effects; D008647:Mesocricetus; D051379:Mice; D008970:Molecular Weight; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens