An estimate of genetic risk from 8-methoxypsoralen photochemotherapy

A method based on a combination of cell culture and pharmacokinetic data is explored as a way of estimating the possible genetic risk to man from a mutagenic chemical. 8-methoxypsoralen, which is given to psoriasis patients as part of a photochemotherapy regime, is used, since it represents a 'real-life' situation and possesses properties that make it particularly amenable to this approach. It is concluded that treatment of males for a mean period of 10 years before their spermatozoa were involved in conception would increase the gene mutation rate in the male germ line by a factor of 0.00125. The implications of this for the incidence of sex-linked and dominant disease in man are elaborated and the assumptions and limitations are set out. The fragility of the estimates is emphasized.