Our laboratory has been examining the mechanisms whereby chemicals produce mutagenicity in short-term in vitro assays yet fail to produce
carcinogenesis in 2-year rodent bioassays. Previous studies indicated that some mutagenic hepatocarcinogens increased cell proliferation in the target organ, the liver, while other structurally related
mutagens that were noncarcinogenic failed to do so. We demonstrate in this report that another mutagenic
carcinogen, tris(2,3-dibromopropyl phosphate), increased cell proliferation that was localized in the outer medulla of the kidney. This was also the target site for
carcinogenesis in a 2-year bioassay and is another example of the association between chemically induced cell proliferation and
carcinogenesis. This study also reports the absence of increased cell proliferation in the liver or kidney after exposure in the diet to the mutagenic
organophosphate insecticides dimethoate,
dioxathion, and
dichlorvos following dietary exposure for 2 weeks at the same dose levels and routes of exposure that did not increase the
tumor incidence in either organ in 2-year
carcinogenesis assays. The present studies support the tenet that chemically induced cell proliferation may be a necessary prerequisite for chemical
carcinogenesis, since in rat liver and kidney there was neither cell proliferation after 2 weeks nor
tumor development after 2 years dietary exposure to the mutagenic
organophosphate insecticides dimethoate,
dioxathion, and
dichlorvos.