Brevetoxin forms covalent DNA adducts in rat lung following intratracheal exposure.

Abstract

BACKGROUND:

Human exposure to brevetoxins produced by the red tide organism, Karenia brevis, is an increasing public health concern. Using in vitro exposure of rat liver cells to brevetoxin B (PbTx-2), the primary toxin product of K. brevis, we previously showed that it formed C(27,28)-epoxy brevetoxin metabolites capable of covalently binding to nucleic acids, a common initiation step for carcinogenesis.

OBJECTIVE:

This study was undertaken to evaluate nucleic acid adduction in lung following in vitro and in vivo brevetoxin exposures.

METHODS:

To clarify reactions of brevetoxin epoxide with DNA, we analyzed reaction products of PbTx-6 (a C(27,28) epoxide metabolite of brevetoxin B) with nucleosides. We also analyzed adducts from nucleic acid hydrolysates of isolated rat lung cells treated with PbTx-2 or PbTx-6 in vitro and lung tissue from rats after intratracheal exposure to PbTx-2 or PbTx-6 at 45 microg toxin/kg body weight.

RESULTS:

Our results indicate that PbTx-2 forms DNA adducts with cytidine after treatment of isolated lung cells, and forms DNA adducts with adenosine and guanosine after intratracheal exposure.

CONCLUSIONS:

These results are consistent with metabolic activation of highly reactive brevetoxin intermediates that bind to nucleic acid. These findings provide a basis for monitoring exposure and assessing the hazard associated with depurination of brevetoxin-nucleotide adducts in lung tissue.

• Authors: Faisal F Y Radwan, John S Ramsdell
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 116 Issue 7 Pg. 930-6 (Jul 2008) ISSN: 0091-6765 [Print] United States
• PMID: 18629316 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA Adducts
• Marine Toxins
• Oxocins
• brevetoxin B
• DNA

Topics

• Animals
• DNA (metabolism)
• DNA Adducts (metabolism)
• DNA Damage
• Dinoflagellida
• In Vitro Techniques
• Lung (cytology, drug effects, metabolism)
• Marine Toxins (toxicity)
• Oxocins (toxicity)
• Rats