Paperβ-Carotene-mediated inhibition of a DNA adduct induced by 7,12-dimethylbenz(a)anthracene and 7-hydroxymethyl-12-methylbenz(a)anthracene in mouse mammary gland in vitro

Add time:09/01/2019    Source:sciencedirect.com

The influence of β-carotene on the formation of DNA-adducts induced by 7,12-dimethylbenz(a)anthracene (DMBA) and 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA) during transformation of mouse mammary cells in organ culture was analysed. Treatment with β-carotene (10−8–10−5 mol/l) caused inhibition (48.8–94.4%) of an adduct (VI), which was detectable in DNA samples from DMBA-treated mammary glands. Out of six adducts, derived from further analysis of DNA samples from 7-OHM-12-MBA-treated glands, adduct f eluted in the same fraction as adduct (VI), indicating these adducts were analogous. Likewise, adduct f was also inhibited by β-carotene. Boronate chromatographic analysis revealed this particular adduct was a syn-dihydrodiol epoxide product. Adduct inhibition was detectable both at the start and after DMBA treatment. α-Tocopherol and canthaxanthin were ineffective in inhibiting adducts. It is reasonable to conclude that β-carotene-mediated modification of adducts is associated with the inhibition of a syn-adduct, which is derived from further metabolism of a 7-OHM-12-MBA intermediate.

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