TY - JOUR
T1 - Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis
T2 - Maternal diets rich in indole-3-carbinol versus sulforaphane
AU - Shorey, Lyndsey E.
AU - Madeen, Erin P.
AU - Atwell, Lauren L.
AU - Ho, Emily
AU - Löhr, Christiane V.
AU - Pereira, Clifford B.
AU - Dashwood, Roderick H.
AU - Williams, David E.
N1 - Funding Information:
The authors would like to thank the staff of the Laboratory Animal Resource Center and the Cancer Chemoprevention Core Labs at Oregon State University. We greatly appreciate the experimental guidance provided by Lisbeth Siddens and the assistance of David Strickland, Rachel Azevedo, Elyssa Ridinger, and David Sampson with animal husbandry and sampling. This study was made possible, in part, by contributions from The Linus Pauling Institute at Oregon State University.
Funding Information:
This work was supported primarily by PHS through the National Institutes of Health grant P01 CA90890; L.E.S. was also supported through T32 ES07060; E.P.M. was also supported by the T32 grant and by P42 ES016465. This study utilized Core facilities made available through the NIEHS Environmental Health Science Center, P30 ES00210, and the NIEHS Superfund Research Program, P42 ES016465.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15. mg/Kg B.W. of dibenzo[. def,. p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000. ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400. ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500. ppm I3C and 600. ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period.
AB - Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15. mg/Kg B.W. of dibenzo[. def,. p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000. ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400. ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500. ppm I3C and 600. ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period.
KW - Indole-3-carbinol
KW - Polycyclic aromatic hydrocarbon
KW - Sulforaphane
KW - T-cell lymphoblastic lymphoma
KW - Transplacental
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UR - http://www.scopus.com/inward/citedby.url?scp=84877351328&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2013.02.016
DO - 10.1016/j.taap.2013.02.016
M3 - Article
C2 - 23566957
AN - SCOPUS:84877351328
SN - 0041-008X
VL - 270
SP - 60
EP - 69
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 1
ER -