Mutagenic and carcinogenic potency indices and their correlation.
We have analyzed a significant number of studies existing in the literature, in which the ability of different short-term tests for predicting carcinogenicity in rodents was investigated. We have separated these studies into two groups. In the better known group of studies, qualitative predictivity was investigated (sensitivity and specificity). In the second group of studies (analyzed in greater detail), positive results were examined for the correlation between carcinogenic potency and potency of response in a given short-term test. There is substantial agreement between qualitative and quantitative predictivity; both appear to be situated between a low and moderate level. We have analyzed the interesting possibility of using the quantitative approach not only for positive data but for combined positive and negative data as well. We have stressed that short-term tests of genotoxicity should be asked to predict only initiation and irreversible alterations in the genome and not to predict a combination of these events, including promotion and modulation of differentiation. Even with regard to only initiation, genotoxicity data should be related to comparative metabolism, as well as to considerations of the significance of different end points and structure-activity relationship data. In conclusion, the information coming from short-term tests of genotoxicity is probably useful but should be used in conjunction with other types of information and only for predicting one particular class of events in the entire process of carcinogenesis.
Parodi
S
S
Istituto di Oncologia Clinica e Sperimentale, Università di Genova, Italy.
Taningher
M
M
Romano
P
P
Grilli
S
S
Santi
L
L
D015197:Carcinogenicity Tests / Q000706:statistics & numerical data*; D006801:Humans; D009152:Mutagenicity Tests / Q000706:statistics & numerical data*; D012306:Risk