Transplacental lung carcinogenesis: molecular mechanisms and pathogenesis

Toxicology and Applied Pharmacology
M S Miller

Abstract

A wide variety of studies in both animal models and human populations have demonstrated age-related differences in the susceptibility of the developing organism to environmentally prevalent toxicants. While this differential susceptibility has been clearly established, the mechanistic basis for these age-related differences is still poorly understood. The developing fetus utilizes many of the same metabolic and signaling pathways as adult organisms in responding to environmental agents. However, it is becoming increasingly evident that the fetus is not a "little adult" and exhibits unique biochemical responses and gene expression profiles to chemical and physical agents. Because of the rapid growth and developmental changes that occur during gestation, the fetus represents a particularly challenging research subject as a result of the dynamic alterations that occur in gene expression pathways as gene systems are activated or repressed during specific stages of development. Thus, an understanding of the mechanism(s) that render the developing organism more or less susceptible to specific carcinogenic agents is crucial for both regulatory decisions regarding the determination of safe levels of toxic chemicals released into the en...Continue Reading

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