Low dose Carcinogenesis Low dose Anticarcinogenesis Hormesis can be seen in the same animal species Richard Wilson, Harvard University Frank Pompei, Exergen Amherst, MA Tuesday, June 11th 2002

Regulatory posture for 30 years If an increase in tumors in any site is seen after administration of a chemical, label it carcinogenic and ban it. This has led experimentation e.g. NTP

Choose most sensitive gender/species Ignore anticarcinogenic effects Allow ad-libitum feeding (simpler and “more sensitive” )

Sir Richard Peto and others; if the cancer is identical to one that occurs naturally, adding a small dose is (differentially) linear (Taylor’s theorem) But what do data say?

It has long been known that alcohol consumption displays hormetic effects (reduction in mortality at low doses and increase in high doses) This is attributed to addition of two effects: reduction in incidence of stroke increase in cancer (and antisocial behavior)

Percentage of chemicals classified as carcinogens.

Percentage of chemicals classified as anticarcinogens

About 5% of cases show anticarcinogenic responses in one site and carcinogenic responses in another. They add to what is seen in alcohol

Carcinogenic responses are easiest to see when there is an increase in rare tumors Anticarcinogenic responses can only be seen as a reduction in common tumors. The sum will display hormesis even if each is individually linear with dose

Schematic picture showing how this leads to hormesis

Kociba’s data on dioxin

Slide of well known data on bladder and on liver

Megamouse data

Science only progresses by (however tentatively) believing data Do we believe the lowest doese data on Dioxin (Kociba et al? Do we believe the lowest dose data from the megamouse study? If not why does not someone repeat the data?

Acknowledgments to many collaborators over the years particularly EAC Crouch Gay Goodman Igor Linkov George Gray