beta-carotene and 7-hydroxymethyl-12-methylbenz(a)anthracene

The influence of beta-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 beta-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 beta-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. alpha-Tocopherol and canthaxanthin were ineffective in inhibiting adducts. It is reasonable to conclude that beta-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.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Chromatography, High Pressure Liquid; DNA; DNA Adducts; Female; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C