Chemoprotective properties of chlorophyllin against vinyl carbamate, p-nitrophenyl vinyl ether and their electrophilic epoxides.
Chlorophyllin (CHL), a water-soluble sodium and copper derivative of chlorophyll, has been shown to be a strong antimutagen in several test systems, but its mechanism of antimutagenic action is largely unknown. In the present study, we have found the protective properties of CHL against vinyl carbamate, p-nitrophenyl vinyl ether and their electrophilic epoxides. CHL exhibited dose-related inhibition of his+ reversion in Salmonella typhimurium TA 1535 induced by these mutagens. Formation of DNA adducts from vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO) was also markedly attenuated in the presence of CHL. Oral administration of CHL prior to the topical application of each of the above carcinogens resulted in significant reduction in both incidence and multiplicity of skin tumors in mice. The effective protection by CHL against VCO and NPO suggest that its formation of inactive complexes with these carcinogens is mediated by mechanisms other than pi-pi interactions.
Park
K K
KK
Department of Biochemistry, College of Medicine, Yonsei University, Seoul, Korea.
Surh
Y J
YJ
Miller
J A
JA
D000818:Animals; D016587:Antimutagenic Agents / Q000378:metabolism / Q000494:pharmacology*; D002735:Chlorophyllides / Q000378:metabolism / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D010212:Papilloma / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000187:drug effects; D012878:Skin Neoplasms / Q000517:prevention & control*; D014520:Urethane / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D014753:Vinyl Compounds / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016587:Antimutagenic Agents; D002735:Chlorophyllides; D018736:DNA Adducts; D004852:Epoxy Compounds; D014753:Vinyl Compounds; D014520:Urethane; C017963:vinyl carbamate; C047678:(4-nitrophenyl)vinyl ether; C007020:chlorophyllin