Carcinogens potency

The purpose of this eornpuLer project is Lo examine several polynuclear aromatic hydrocarbons and to relate their electron density patterns to their carcinogenic activity. If nucleophilic binding to DN.A is a significant step in blocking the normal transcription process of DN.A, electron density in the hydrocarbon should be positively correlated to its carcinogenic potency. To begin with, we shall rely on clinical evidence that benzene, naphthalene, and phenanthrene... 

Carcinogen Potency Factor (CPF) A CPF is the slope of the dose-response cun e at very low exposures. The dimensions of a CPF, are expressed as the iin erse of daily dose (mg/kg-day)". ... 

Slope Factor The slope factor is used to estimate an upper-bound lifetime probabilit) of an individual dc cloping cancer as a result of exposure to a particular le cl of a potential carcinogen. Also sec Carcinogen Potency Factor (CPF)... 

Qi — The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure. The q, can be used to calculate an estimate of carcinogenic potency, the incremental excess cancer risk per unit of exposure (usually pg/L for water, mg/kg/day for food, and pg/m for air). 

There appears now to be ample evidence that the variations in carcinogenicity among the nitrosamines are systematically and rationally related to structure and that several Indices of carcinogenic potency can be used as indices of biological response for the generation of quantitative structure-activity models (11-17). 

The experiments with deuterium-labeled nitrosamines illustrate two important points. One is that oxidation of nitrosamines takes place at more than one position in the molecule, and the outcome of the balance of such competing reactions probably is the determinant of carcinogenic potency. The second is that the reason for the failure of carcinogenesis to be mirrored in many cases by the microsomally activated bacterial mutagenicity is that there can be several metabolic steps leading to formation of the proximate carcinogenic agent and not all of these need necessarily involve microsomal enzymes. ... 

Note 1 - DSSTox carcinogenic potency DBS MultiCellCall 2 - DSSTox carcinogenic potency DBS Rat 3 - DSSTox carcinogenic potency DBS SingleCell ... 

Loew CH, Rebagliati M, Poulsen M. 1984. Metabolism and relative carcinogenic potency of chloroethanes a quantum chemical structure-activity study. Cancer Biochem Biophys 7 109-132. 

Piegorsch WW, Hoel DG. 1988. Exploring relationships between mutagenic and carcinogenic potencies. Mutat Res 196(2) 161-175. 

---