Chemopreventive properties of chlorophyllin: inhibition of aflatoxin B1 (AFB1)-DNA binding in vivo and anti-mutagenic activity against AFB1 and two heterocyclic amines in the salmonella mutagenicity assay
Chlorophyllin (CHL), a sodium/coper derivative of chlorophyll, has beenused to treat a number of human conditions with no tixic effects being reported. Recent studies have described the anti-mutagenic activity of CHL in several short-term genotoxicity assays; however, this compound has not been reported to inhibit carcinogen-DNA binding in vivo, and it as yet to be evaluated as an anti-carcinogen in any spacies. The chemopreventive properties of CHL were studied in trout using inhibition of aflatoxin B1 (AFB1)-DNA binding as an end-point. Chlorophyllin and AFB1were co-administered in the diet, and carcinogen-DNA binding levels were determined in liver after 1, 3, 5 and 7 days. Linear increased in AFB1,-DNA binding occurred with time of treatment at each CHL dose level (0, 500, 1000, and 2000 p.p.m.). Each increase in CHL doese produced a concomitant decrease in AFB1-DNA binding was inhibited by 70%. These resulted suggest that CHL should be a potent inhibitor of AFB1-induced hepatocarcinogenesis in this model. In the Salmonella assay, CHL exhibited potent anti-mutagenic activity against AFB1 and two heterocyclic amines when incubated in the presence of trout liver activation systems. CHL also inhibited the mutagenic activity of AFB1-8,9-epoxide in the absence of metabolic activation system. Dietary CHL substantially inhibited liver AFB1-DNA binding in vivo, even when AFB1 was given by i.p. injection to avoid direct AFB1-CHL interaction in the diet or gt. Collectively, these studies support a CHL inhibitory mechanism involving complex formation with the carcinogen in the gut coupled with electrophile scavenging or further compelxing in the target organ.