Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: the importance of in utero vs. lactational exposure.
The fetus and neonate cannot be viewed as "little adults"; they are highly sensitive to toxicity from environmental chemicals. This phenomenon contributes to the fetal basis of adult disease. One example is transplacental carcinogenesis. Animal models demonstrate that environmental chemicals, to which pregnant women are daily exposed, can increase susceptibility of the offspring to cancer. It is uncertain to what degree in utero vs. lactational exposure contributes to cancer, especially for hydrophobic chemicals such as polyhalogenated biphenyls, ethers, dioxins, furans, etc., which can partition into breast milk. We developed a pregnant mouse model in which exposure to the polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), during late gestation, produces an aggressive T-cell lymphoma in offspring between 3 and 6 months of age. Survivors exhibit multiple lung and liver (males) tumors. Here, we adopt a cross-foster design with litters born to dams treated with DBP exchanged with those born to dams treated with vehicle. Exposure to DBP in utero (about 2 days) produced significantly greater mortality than residual DBP exposure only through breast milk (3 weeks of lactation). As previously observed pups in all groups with an ahr(b-1/d) ("responsive") genotype were more susceptible to lymphoma mortality than ahr(d/d) ("non-responsive") siblings. At termination of the study at 10 months, mice exposed in utero also had greater lung tumor multiplicity than mice exposed only during lactation. Our results demonstrate that short exposure to DBP during late gestation presents a greater risk to offspring than exposure to this very hydrophobic PAH following 3 weeks of nursing.
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331-7301, USA.
David J
DJ
Castro
Christiane V
CV
Löhr
Kay A
KA
Fischer
Clifford B
CB
Pereira
David E
DE
Williams
D000818:Animals; D001580:Benzopyrenes / Q000493:pharmacokinetics / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007774:Lactation; D008175:Lung Neoplasms / Q000139:chemically induced*; D016399:Lymphoma, T-Cell / Q000139:chemically induced*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*
D001580:Benzopyrenes; D002274:Carcinogens, Environmental; C041517:dibenzo(a,l)pyrene