Promutagen activation in partially hepatectomized mice

Area of Science:

• Toxicology
• Hepatology
• Genetics

Background:

• Aflatoxin B1 (AFB1) is a potent mutagen and carcinogen requiring metabolic activation.
• Liver enzymes, particularly those in the S-9 fraction, are crucial for metabolizing AFB1.
• Partial hepatectomy (PH) induces liver regeneration, potentially altering enzyme expression and activity.

Purpose of the Study:

• To investigate the effect of partial hepatectomy (PH) on the mutagenic activity of aflatoxin B1 (AFB1).
• To compare the metabolic activation of AFB1 by liver S-9 fractions from control and PH mice using the Ames test.

Main Methods:

• The Ames Salmonella/microsome assay was employed to assess mutagenicity.
• Liver S-9 fractions were prepared from control, sham-operated, Aroclor 1254-induced, and partially hepatectomized (PH) mice at 42h and 148h post-surgery.
• Mutagenic activity of AFB1 was evaluated using Salmonella typhimurium strain TA100.

Main Results:

• Liver S-9 preparations from PH mice exhibited significantly greater capacity to induce AFB1 mutagenic activity compared to controls.
• This enhanced mutagenic activity was observed at both 42h and 148h following PH.
• Aroclor 1254-induced S-9 showed lower AFB1 mutagenic activity than S-9 from PH mice.

Conclusions:

• Partial hepatectomy in mice leads to an enhanced metabolic activation of aflatoxin B1.
• The regenerating liver exhibits altered enzymatic profiles that increase the mutagenicity of AFB1.
• These findings highlight the dynamic nature of xenobiotic metabolism during liver regeneration.