Metabolic activation of aflatoxin B1 by human placental microsomes
M Sawada1, R Kitamura, T Norose
1Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Abstract:
The metabolic activation of aflatoxin B1 by human placental microsomes was studied. Aflatoxin B1 showed relatively high mutagenic activity in Ames test when incubated with human placental microsomes. Addition of alpha-naphthoflavone or aminoglutethimide, known inhibitors of cytochrome P450 1A and P450 19, respectively, into the test system partially inhibited the mutagen-producing activity. It was suggested that the activation of aflatoxin B1 in human placental microsomes is mediated by at least these two forms of cytochrome P450.
Insights
Human placental microsomes activate aflatoxin B1, increasing its mutagenic potential. This activation involves cytochrome P450 enzymes, specifically P450 1A and P450 19.
Area of Science:
- Toxicology
- Biochemistry
- Pharmacology
Background:
- Aflatoxin B1 is a potent mycotoxin with known mutagenic and carcinogenic properties.
- The human placenta plays a crucial role in fetal development and can be exposed to various xenobiotics.
Purpose of the Study:
- To investigate the metabolic activation of aflatoxin B1 by human placental microsomes.
- To identify the specific cytochrome P450 enzymes involved in this activation process.
Main Methods:
- Incubation of aflatoxin B1 with human placental microsomes.
- Assessment of mutagenic activity using the Ames test.
- Inhibition studies using alpha-naphthoflavone (CYP1A inhibitor) and aminoglutethimide (CYP19 inhibitor).
Main Results:
- Human placental microsomes exhibited significant aflatoxin B1-activating capability, leading to high mutagenic activity in the Ames test.
- The mutagen-producing activity was partially reduced by alpha-naphthoflavone and aminoglutethimide.
- These findings indicate the involvement of cytochrome P450 1A and cytochrome P450 19 in the metabolic activation.
Conclusions:
- Human placental microsomes metabolically activate aflatoxin B1, contributing to its mutagenicity.
- Cytochrome P450 1A and cytochrome P450 19 are implicated as key enzymes in the activation pathway.
- This study highlights potential risks associated with aflatoxin B1 exposure during pregnancy.
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