Perinatal and multigenerational effect of carcinogens: possible contribution to determination of cancer susceptibility

Abstract

Perinatal exposure to carcinogens may contribute to the determination of susceptibility to cancer in two situations: a) exposure in utero of embryonal or fetal somatic cells to carcinogens, and b) prezygotic exposure of the germ cells of one or both parents to carcinogens. Epidemiological as well as experimental studies demonstrate that exposure to carcinogens in utero increases the occurrence of cancer postnatally. Studies with experimental animals suggest that prezygotic exposure of germ cells to carcinogens can result in an increased incidence of cancer not only in immediate but also in subsequent generations. Although several studies suggest a transgeneration effect of carcinogens in human populations, the evidence cannot yet be considered conclusive. In particular, while some hypotheses can be advanced, the mechanism(s) by which increased susceptibility or predisposition to cancer may be transmitted via the germ cells has not yet been clarified. In conjunction with exposure both in utero and prezygotically, it is important to consider postnatal exposure to possible tumor-promoting agents. Results from experimental animals suggest that oncogenes can be activated transplacentally, and human studies indicate that tumor-suppressor gene inactivation may be involved in the transgenerational effect of carcinogens.