beta-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.
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.
Das
S K
SK
Third Hospital, Beijing Medical University, People's Republic of China.
Jia
T Z
TZ
Bandyopadhyay
A M
AM
Banerjee
M R
MR
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D019207:beta Carotene
C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D018736:DNA Adducts; D019207:beta Carotene; D002338:Carotenoids; C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA