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La conversión de B-ADN a Z-ADN inducida por la sal fue inhibida por la aflatoxina B1

A Nordheim, W M Hao, G N Wogan

Science (New York, N.Y.)

|March 25, 1983

Resumen

Los adductos carcinógenos de la aflatoxina B1 inhiben significativamente la conversión estructural del ADN-B al ADN-Z en polímeros. Este efecto de inhibición se observó incluso a bajos niveles de unión a la aflatoxina.

Área de la Ciencia:

Biología Molecular Biología Molecular
Genética La genética.
Toxicología Toxicología.

Sus antecedentes:

El ADN existe en varias formas estructurales, incluyendo el B-ADN de la mano derecha y el Z-ADN de la mano izquierda.
La transición de B-ADN a Z-ADN está influenciada por la concentración de sal y la secuencia de ADN.
La aflatoxina B1 es un potente carcinógeno que puede formar adductos con el ADN.

Objetivo del estudio:

Para investigar el impacto de la formación de adductos de aflatoxina B1 en el cambio conformacional del ADN-B al ADN-Z.
Para determinar si el daño al ADN por la aflatoxina B1 afecta la plasticidad estructural del ADN.

Principales métodos:

Se sintetizó un polímero de residuos alternos de desoxiguanina y desoxicitosina.
El polímero fue reaccionado con la aflatoxina B1 para formar aductos.
La conversión inducida por la sal de B-ADN a Z-ADN fue monitoreada antes y después de la modificación de la aflatoxina B1.

Principales resultados:

La formación de adductos de aflatoxina B1 inhibió fuertemente la conversión inducida por la sal del polímero de ADN de B-ADN a Z-ADN.
Este efecto inhibidor fue detectable incluso a bajos niveles de unión a la aflatoxina B1.
La presencia del carcinógeno alteró la capacidad del ADN para adoptar la conformación Z-ADN.

Conclusiones:

El daño al ADN inducido por la aflatoxina B1 puede afectar significativamente la dinámica estructural del ADN.
La formación de adductos de aflatoxina B1 interfiere con la flexibilidad conformacional requerida para la formación de ADN-Z.
Estos hallazgos ponen de relieve un mecanismo potencial por el cual la aflatoxina B1 puede ejercer sus efectos cancerígenos al alterar la estructura del ADN.

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