Trans-generational effects of low dose exposure to POPs on the formation of intestinal lesions in A/J-APC(Min/+) mice
Persistent organic pollutants (POPs) occur in nature and in tissues of both humans and animals. These substances have adverse effects and can be transferred from mother to offspring. Fetuses’ and newborn humans are known to be exposed to relatively high concentrations of POPs through the placenta and mothers milk. In addition, these compounds may induce adverse effects that become evident later in life. Although much is known about POPs, there is little knowledge of how exposure via ingestion in the mother affects the offspring at a later stage in life.
In this experiment we will investigate how the exposure to POPs in mothers affects the formation of intestinal lesions in the offspring. For this we will use up to 44 A/J wildtype females given a diet based on AIN-93 complemented with a low dose of the POP mixture from weaning and throughout pregnancy and lactation. A/J-APC(Min/+) offspring (n=54) will be euthanized at 25 weeks of age and used to investigate the effects on the intestinal tumorigenesis after exposure through the placenta and breast milk.
Few disturbances will be afflicted upon the animals during the experimental period. The diets will be available ad libitum. Additional handling of the animals will only occur during weighing, and is not considered to affect the well-being of the mice. Although in vitro studies are a helpful tool within cancer research, the studies do not enable us to make reliable predictions regarding carcinogenesis. In addition, components of the diet interfere with the environment of the intestine, which is essential for the outcome of this study. After careful consideration, the performance of an animal experiment provides the only possibility to include the entirety of physiological processes while investigating the compounds' effect on carcinogenesis.
The APC(Min/+) mice model is well suited to study the susceptibility for the formation of intestinal lesions, as well as tumor distribution. Due to the similarity between the gene defect in this mice model and in human sporadic colorectal cancer, the model can also be used as a model for carcinogenesis in colorectal cancer in humans.
In this experiment we will investigate how the exposure to POPs in mothers affects the formation of intestinal lesions in the offspring. For this we will use up to 44 A/J wildtype females given a diet based on AIN-93 complemented with a low dose of the POP mixture from weaning and throughout pregnancy and lactation. A/J-APC(Min/+) offspring (n=54) will be euthanized at 25 weeks of age and used to investigate the effects on the intestinal tumorigenesis after exposure through the placenta and breast milk.
Few disturbances will be afflicted upon the animals during the experimental period. The diets will be available ad libitum. Additional handling of the animals will only occur during weighing, and is not considered to affect the well-being of the mice. Although in vitro studies are a helpful tool within cancer research, the studies do not enable us to make reliable predictions regarding carcinogenesis. In addition, components of the diet interfere with the environment of the intestine, which is essential for the outcome of this study. After careful consideration, the performance of an animal experiment provides the only possibility to include the entirety of physiological processes while investigating the compounds' effect on carcinogenesis.
The APC(Min/+) mice model is well suited to study the susceptibility for the formation of intestinal lesions, as well as tumor distribution. Due to the similarity between the gene defect in this mice model and in human sporadic colorectal cancer, the model can also be used as a model for carcinogenesis in colorectal cancer in humans.