Beta-carotene affects gene expression in lungs of male and female Bcmo1 (-/-) mice in opposite directions.
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15'-monooxygenase 1 knockout (Bcmo1 (-/-)) mice, which are-like humans-able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 (-/-) mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 (-/-) mice. Testosterone levels were higher after BC supplementation only in Bcmo1 (-/-) mice, which had, unlike wild-type (Bcmo1 (+/+)) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.
van Helden
Yvonne G J
YG
Human and Animal Physiology, Wageningen University, PO Box 338, 6700 AH Wageningen, The Netherlands.
Godschalk
Roger W L
RW
Swarts
Hans J M
HJ
Hollman
Peter C H
PC
van Schooten
Frederik J
FJ
Keijer
Jaap
J
D000818:Animals; D019587:Dietary Supplements; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012737:Sex Factors; D013256:Steroids / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics*
D013256:Steroids; D019207:beta Carotene; D013739:Testosterone; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase
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