Clinical trials of TCDD.

Abstract

A patent (No. 6,444,698) has been issued recently allowing the use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a promoter blocker of specific, named cancers in men and women as well as multiple cancers measured as total cancers.1 Supporting the patent claim are the Kociba lifetime male and female rat feeding study (Kociba et al. 1978) and three epidemiology studies identified below heretofore regarded as environmental rather than clinical based on the presentation of study data in the literature and/or their design. In this note I would like to utilize attributes associated with TCDD’s activity to recast these epidemiology studies as clinical rather than environmental. These attributes include persistence of TCDD in humans (half-life equals 7.5 years, per Michalek et al. 1996) to a calculable and sufficiently constant TCDD body burden level, and a sufficiently long latency period to measure the effects of a chemical acting as a promoter blocker (Kayajanian 1997). In Kociba, 50 or 49 male and female rats were fed diets of 20, 200, or 2000 ppt TCDD, which does not persist in rats (Fries and Marrow 1975). Eighty-five males and 86 females served as controls. When compared to the respective control, the measure total cancers/animal was always reduced in each exposed group, and significantly reduced (p < 0.01) in each sex at low and mid exposures (Kayajanian 1997). This study establishes TCDD as a potent anticarcinogen in rats. If TCDD behaves as an anticarcinogen in humans as it does in rats, at what stage of cancer creation does TCDD act? If TCDD were to block the final replicative step leading to a cancer diagnosis in humans, one would expect to observe a reduction in expected cancers in short order, say, within a year. If TCDD were to block the promotional step in cancer creation, the cancer reduction would take more time to register — several years, perhaps 5. If TCDD were to block an early step in cancer creation, like initiation, it might take 15, 20, or more years to register the effect as a cancer reduction. These cancer reduction effects should continue for as many years as the TCDD level in man remains sufficient. Of course, many of the exposures to TCDD have occurred in settings with contemporaneous exposures to many other chemicals assumed to act as cancer initiators. Their carcinogenic effects might mask the cancer preventative effects of TCDD 15, 20, or more years after the initial exposure to them and TCDD.