Does everything "cause" cancer: an alternative interpretation of the "carcinogenesis" bioassay

Abstract

R. S. Chhabra, J. Haseman, A. Hall, and C. Baskin (Fundam. Appl. Toxicol. 11, 685-690, 1988) have raised the question of whether the apparent antitumorigenic effect of 4-hexylresorcinol suggests its possible use as an antineoplastic agent. In response to that paper, it is noted that over 20% of the compounds subjected to the "carcinogenesis" bioassay of the NCI/NTP program show apparent antitumorigenic effects of a similar sort. A thought experiment is proposed that shows that any compound subjected to these test conditions should produce a shift in patterns of tumors, regardless of whether the compound is a true "carcinogen" or a true "antineoplastic" agent. This thesis is illustrated with an alternative statistical analysis of six AZO dye studies that were conducted in the same lab during the same period, and the existence of apparent effects for three other other relatively innocuous substances is noted. Short-term experiments are proposed to test this thesis. Finally, the implications of this thesis on the interpretation of "carcinogenesis" bioassays is examined.