How do Heterocyclic Amines, Amino Acid Pyrolysates, Inhibit DNA Repair

Abstract

Heterocyclic amines (HCAs) and β-carbolines, carcinogenic substances, are produced when amino acids and creatine in food react in a high-temperature environment. Some of them are reported to be rodent carcinogens and potent mutagens and to have co- clastogenic effects by inhibiting the incision step in DNA excision repair. In this study, we studied the mechanisms of their inhibition of DNA excision repair. HCAs (Trp-P- 1, IQ, and Me IQ) suppressed comet responses by UV. Since they were antagonistic to novobiocin that is an inhibitor of ATPase subunit of topoisomerase acting the in the incision step of excision repair and the removal of cyclobutane pyrimidine dimers (CPDs) induced by UV was suppressed by Trp-P-1 and IQ, they were considered to inhibit the incision step of excision repair. On the contrary, β-carbolines (harman and norharman) enhanced comet responses by UV. Since they were antagonistic to cytosine-1-β-D arabinofuranoside that is an inhibitor of DNA polymerase acting in the re-synthesis step of excision repair, they were considered to inhibit the re-synthesis step of excision repair. Based on thesis results, HCAs and β-carbolines were concluded to inhibit the incision and re-synthesis steps of excision repair, respectively.