ELEVATION OF SERUM PHASE-III ENZYMES BY ANTICARCINOGENIC ENZYME INDUCERS - MARKERS FOR A CHEMOPROTECTED STATE

Inducers of Phase II enzymes, already consumed by humans as food addit ives, medicines or as constituents of vegetables, can prevent experime ntal carcinogenesis. Since protection is neither carcinogen- nor organ -specific, clinical trials are already underway to establish the effic acy of 'anticarcinogenic enzyme inducers' (i.e. oltipraz). However, ef ficient and cost-effective assays to establish the dose wherein a puta tive anticarcinogen can raise Phase II enzyme levels are lacking. We t ested the proposal that serum Phase II enzyme activities would be depe ndent on relative tissue levels by measuring quinone reductase and glu tathione S-transferase activities in sera of mice treated,vith dietary 2(3)-tert-butyl-4-hydroxyanisol (BHA) or dimethyl fumarate. Serum act ivities were significantly elevated in animals with increased tissue s pecific activities of these Phase II enzymes. Increasing concentration s of BHA in the diet from 0.05-0.5% increased hepatic specific activit ies of both QR and GST from two to six-fold, and increases in serum ac tivities were well correlated to increases observed in the liver (r(2) greater than or equal to 0.95). There was no evidence for an elevatio n of serum alanine aminotransferase levels. Thus, in the absence of se rological evidence for hepatocellular damage, increased serum Phase II enzyme activities can be correlated to tissue levels. Our results sug gest that similar assays tailored to human sera will not only be usefu l in the execution of chemoprevention trials, but also to assess the r ole that Phase II enzyme induction plays in the prevention of cancer b y fruits and vegetables.