Today, there is a large body of evidence on in utero carcinogenesis in animal models (Table 19.1). However, the mechanisms underlying these processes are poorly understood. It is possible that the time window of carcinogenesis is dependent on activation of some compounds into active metabolites by either placenta (see Chapter 4) or target cells in the fetus. For a complete reference on existing experimental studies the reader may wish to refer to Schuller's recent book.

In this chapter we will focus on evidence existing today of transplacental human carcinogenicity, including proven as well as yet to be proven agents.

Diethylstilbestrol (DES)

In 1971, Herbst and colleagues published the first series of adenocarcinoma of the vagina in adolescent females exposed to the hormone during the first 10 weeks of fetal life. The adenosis, cervical erosions and ridges were believed at that time to occur at very high frequency of exposed fetuses. However, as shown subsequently by the registry of DES cases, the risk of this cancer was less than one in thousands! The causation was probably detected owing the extreme rarity of this tumor among adolescent girls.

On the other hand, morphological changes in the vaginal epithel could be detected in as many as 34% of exposed girls (compared to 0.4% in the general population). As shown in Table 18.1, similar changes could be reproduced in animal models. With the removal of DES from the market and the disappearance of this syndrome, it still remains an important milestone in understanding the molecular and cellular mechanisms leading to late carcinogenesis.