EFFECT OF SELECTED ANTIMUTAGENS ON THE GENOTOXICITY OF ANTITUMOR AGENTS

Cyclophosphamide (CP), bleomycin (BL), doxorubicin (DOX) and cisplatin (CISP) are potent antitumor drugs used worldwide against many forms o f human cancer. As with most such agents, there can be physiological s ide-effects and the possible induction of mutations and other genotoxi c effects in non-tumor cells. It is common for patients to ingest a ho st of food supplements to diminish the discomforting side-effects of t herapy. Because these food supplements are often also rich in antimuta gens that could also affect the biological efficacy of the antitumor d rugs, we investigated if such antimutagenic agents were indeed antimut agenic to these antitumor drugs. Using the Salmonella/microsome bioass ay, we tested CP, BL, DOX, and CP for mutagenicity in the presence and absence of the antimutagens ascorbic acid (AA), chlorophyllin (CHL) a nd (+)-catechin (CAT). AA was a very effective antimutagen against CIS P and less effective against BL and DOX. It was not antimutagenic to C P. CHL was effective as an antimutagen against all four antitumor drug s, and CAT was a strong inhibitor of DOX mutagenicity, but had little effect on BL, CP and CISP. These data now provide a basis for future i n vivo antitumor/antimutagen combination studies to determine if these antimutagens function in a manner to reduce genetic effects without h aving concomitant effects on intended antitumorogenicity of these ther apeutic agents. (C) 1998 Elsevier Science B.V. All rights reserved.