Inhibition by germ-free status of development of liver and lung tumours in mice exposed neonatally to 7,12-dimethylbenz(a)anthracene: implications in relation to tests for carcinogenicity.

Abstract

AbstractGerm‐free (GF) status significantly “protected” male C3H mice from the early (before 40 weeks) development of liver‐cell tumours in response to 7,12‐dimethylbenz(a)anthracene (DMBA) given shortly after birth. GF status significantly protected C3H mice of both sexes from the early development of adenomas of the lung in response to the same treatment, and may have protected DMBA‐treated C3H female mice from the development of malignant lymphoma, mammary, ovarian and uterine tumours. Age in excess of 80 weeks counteracted the protective effect of GF status. GF status had no consistent effect on the incidence of sarcomas at the site of neonatal injection of DMBA. The fact that a factor as non‐specific as the difference between normal micro‐biological status and GF status may have such a profound effect on the age‐standardized risk of development of lung and liver tumours in mice, suggests that the term “carcinogen” should not be applied to an agent if the only evidence of relevant activity is that it increases the risk of development of either or both these types of tumour in mice. Possible mechanisms, including immunological mechanisms, by which GF status influences the response to DMBA are discussed and the need for further studies is stressed.