Modulation of cytochrome P-450IA1-mediated mutagenicity, DNA binding and metabolism of benzo[a]pyrene by Chinese medicinal herbs. 1993

B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
Department of Natural Science, Graduate School, Loma Linda University, CA 92350.

Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumors. We previously showed that they inhibited mutagenesis, DNA binding and metabolism of benzo[a]pyrene (BaP) and aflatoxin B1 (AFB1) bioactivated by Aroclor 1254-induced rat hepatic S9. The purpose of this study was to investigate the effects of OD and SB on the cytochrome P-450IA1-mediated mutagenicity of BaP in Salmonella typhimurium TA100 using beta-naphthoflavone (beta NF)-induced rat hepatic S9. We also determined the effects of OD and SB on cytochrome P-450IA1-linked ethoxyresorufin O-deethylase (EROD) activity in beta NF-induced hepatic microsomes. In addition, we studied the effects of these two herbs on BaP metabolite binding to calf thymus DNA and using high performance liquid chromatography (HPLC) we investigated the effects of OD and SB on the metabolism of BaP by beta NF-induced S9. Our experimental results showed that OD and SB inhibited the mutagenicity of BaP in the presence of either non-induced or beta NF-induced S9. SB significantly inhibited BaP binding to DNA. These effects correlated with the inhibition of cytochrome P-450IA1-linked EROD activity in beta NF-induced microsomes and with an inhibition of beta NF-induced S9 mediated metabolism of [3H]BaP as determined by HPLC. These results suggest that OD and SB may possess antimutagenic activity by inhibiting P-450IA-mediated metabolism of BaP.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004365 Drugs, Chinese Herbal Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China. Chinese Herbal Drugs,Plant Extracts, Chinese,Chinese Drugs, Plant,Chinese Plant Extracts,Extracts, Chinese Plant,Herbal Drugs, Chinese
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D012486 Salmonella typhimurium A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes PARATYPHOID FEVER. Salmonella typhimurium LT2
D016296 Mutagenesis Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS. Mutageneses
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

Related Publications

B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
September 1985, Biochemistry,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
May 1983, Molecular pharmacology,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
January 1982, Carcinogenesis,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
February 1979, Biochemical Society transactions,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
November 1991, Carcinogenesis,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
October 1998, Carcinogenesis,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
November 1984, Carcinogenesis,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
February 1987, Xenobiotica; the fate of foreign compounds in biological systems,
B Y Wong, and B H Lau, and T Yamasaki, and R W Teel
January 1994, Environmental and molecular mutagenesis,
Copied contents to your clipboard!