Tumors in CF-1 mice exposed for six consecutive generations to DDT.

Abstract

CF-1 minimal inbred mice of 6 consecutive generations (parents, F1-F5) were fed 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (technical DDT) mixed into the diet at dose levels of 2, 10, 50, and 250 ppm for their lifespans. The experiment involved 3987 mice, including DDT-exposed and negative and positive controls. Exposure to all A levels of DDT significantly increased liver tumors (hepatomas) in males (50–55.9% in the 2, 10, and 250 ppm groups and 86% in the 250 ppm DDT groups, compared to 29.5% in controls). In females, hepatoma incidence increased considerably after exposure to 250 ppm DDT (65.5% compared to 4.7% in controls), whereas 10 and 50 ppm DDT only slightly increased the incidence (9 and 13%, respectively). No effect was noted at the level of 2 ppm DDT in females. The average lifespan of males with hepatomas decreased in DDT-treated groups (84 wk at the 250 ppm DDT level, 101–104 wk at the levels of 2, 10, and 50 ppm, as compared to 114 wk in controls). In females, only the highest dose level shortened the average lifespan of hepatoma-bearing mice (94 wk compared to 104 wk in controls). DDT did not alter tumor incidence at sites other than the liver, though an apparent, but not significant, increase in lung tumor incidence was noted at the levels of 2 and 10 ppm DDT. No progressive increase of hepatoma incidence from generation to generation was noted in DDT-treated mice. However, considerable variations in the incidence of tumors of the liver, lungs, and hematopoietic tissue were observed between the generations within each treatment group, including controls. One metastasizing hepatoma was found in controls and 13 in 4 DDT-treated groups. Malignant liver tumors, tentatively termed “hepato-blastomas,” also occurred, with a slightly increased incidence in the 10 and 50 ppm groups (3.9 and 3.1%, respectively, as compared to 0.9% in controls) and a significant increase in the 250 ppm group (7.1%). Ten of 56 tumors of this type found in DDT-treated mice metastasized to the lungs.