From chimney sweeps to astronauts: cancer risks in the work place: the 1998 Lauriston Taylor lecture.

Percival Pott, in 1775, was the first to note an association between overt cancer and a carcinogen in the work place when he astutely observed an elevated incidence of scrotal cancer in small boys who assisted chimney sweeps. In their "workplace" astronauts and crew of high altitude jet-liners are exposed, not only to low linear energy transfer (LET) radiation but also to HZE (high energy + high atomic number) particles and to neutrons-for which no human epidemiological data exist. The current system of radiation protection is based on risk estimates from low LET radiations, delivered in large doses and at high dose-rate, coupled with the assumption of a linear no-threshold model. In extrapolating to low doses and dose-rates, and to high LET radiations, it would be helpful if the mechanisms of radiation carcinogenesis were known. Unfortunately that is not the case, though progress has been made toward that end. Many human leukemias and lymphomas appear to be due to specific chromosomal translocations, while solid tumors usually involve multiple mutations in oncogenes, deletions in suppressor genes, and/or chromosomal rearrangements. Genomic instability and immortality are hallmarks of cancer and it is attractive to hypothesize that this is due to a mutation in a gene or genes responsible for the stability of the genome. Examples abound of a small DNA change inactivating a gene and leading to major biological consequences. This could result from a single particle, especially a HZE particle, or a recoil proton from the absorption of a neutron. In this context the assumption of a threshold is hazardous, and the linear no-threshold hypothesis still appears to be prudent and conservative.