Procarcinogen activation by rat and human mammary extracts

: Sprague-Dawley rat mammary gland is extremely sensitive to tumorigenesis by single or multiple doses of several polycyclic aromatic hydrocarbons. We obtained quantitative data on the in vitro mutagenic activation of several procarcinogens by 9000 g supernatant fraction (S9) from rat mammary gland using the Ames test. Mutagenic activation was shown to be dependent on a nicotinamide adenine dinucleotide phosphate (NADPH) generating system. An S9 preparation from mammary tissue of lactating Sprague-Dawley rats was shown to activate 2-aminoanthracene (2-AA). A polychlorinated biphenyl mixture of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given to rats greatly raised the specific activity (revertant TA98 colonies/mg S9 protein) of the mammary tissue using 2-AA as a test carcinogen, and permitted detection of 2,4-diaminoanisole (DAA) and 2,7-diaminofluorene (DAF) activation. Procarcinogens 2-aminofluorine (2-AF), benzo[a]pyrene (BP) and aflatoxin (AFL) B1 were not detectably activated by mammary gland. Mutagenesis produced in mammary S9 activation of 2-AA, DAA or DAF was significantly inhibited by alpha-naphthoflavone (alpha NF) but was inhibited minimally by metyrapone (MP). Human mammary tumor cell lines (734B, SkBr3, MDA-MD-330) possessed inducible procarcinogen metabolizing activities similar to those found in S9 of rat mammary tissue. We demonstrated a simple and convenient use of the Ames test to characterize activation of many potential mutagens and carcinogens for mammary gland. When a test compound such as 2-AA was used, selective enzyme induction and inhibition was demonstrated.