J Korean Assoc Oral Maxillofac Surg.  2000 Apr;26(2):137-145.

An Experimental Study on the Chemopreventive effect of Chlorophyllin in Hamster Cheek Pouch Tumor induced by 7, 12-dimethylbenz[a]anthracene

• Yoon KH

Abstract

Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and 3.7+/-0.6 to 1.4+/-0.3, respectively. The occurrence of histidine revertant by 20 micromole DMBA was inhibited 25.6 to 81.7% by 1 to 5 microM CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

Keyword

Chemoprevention; DMBA; Mutation; Non-isotopic restriction fragment length polymorphism Tumor yield

MeSH Terms

9,10-Dimethyl-1,2-benzanthracene
Animals
Carcinogenesis
Carcinogenicity Tests
Cheek*
Chemoprevention
Chlorophyll
Codon
Copper
Cricetinae*
Drug Therapy
Genes, ras
Histidine
Mutagenicity Tests
Mutation Rate
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Sodium
9,10-Dimethyl-1,2-benzanthracene
Chlorophyll
Codon
Copper
Histidine
Sodium