International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 18. Review of the genotoxicity and carcinogenicity of antischistosomal drugs; is there a case for a study of mutation epidemiology? Report of a task group on mutagenic antischistosomals.
One of the interests of ICPEMC is to identify situations in which the possible induction of inherited defects in man by mutagen exposure could actually be studied. The large-scale use of mutagenic drugs in field programmes against schistosomiasis, mainly during the 1970's, was considered a possible case. An ICPEMC task group approached the problem by (1) updating the genetic toxicology data base for antischistosomal drugs, and (2) reviewing possible study areas. Expertise was combined from genetic toxicology, mutation epidemiology and tropical medicine. It was considered that: (a) if any, hycanthone would be the most appropriate candidate drug for study; (b) it would be virtually impossible to meet the basic requirements of an appropriate mutation epidemiology study, in endemic countries; (c) as more defined genetic endpoints would be selected (e.g. sentinel phenotypes) the required large sample sizes would seem prohibitive, since documentation on past programmes is limited and local demography would render the reliable tracking of substantial numbers of offspring of treated persons an almost impossible task; (d) in most endemic countries proper diagnosis and registration of inherited defects is largely lacking; (e) the problems encountered in demonstrating inherited effects in humans after heavy or chronic exposure to established animal mutagens such as ionizing radiation and cancer chemotherapy, in combination with the ambiguous nature of the animal germ cell data with hycanthone, do not particularly warrant large expectations; (f) since non-mutagenic antischistosomal drugs are now in use, the problem is academic and of low priority in the endemic countries whose medical and research resources are often limited. Thus, studying offspring of hycanthone-treated people to demonstrate the mutagenic potential of the drug in man is not a viable enterprise.
Kramers
P G
PG
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Gentile
J M
JM
Gryseels
B J
BJ
Jordan
P
P
Katz
N
N
Mott
K E
KE
Mulvihill
J J
JJ
Seed
J L
JL
Frohberg
H
H
D000818:Animals; D002273:Carcinogens; D030342:Genetic Diseases, Inborn / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D009153:Mutagens; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology; D012552:Schistosomiasis / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D012556:Schistosomicides / Q000627:therapeutic use / Q000633:toxicity*
D002273:Carcinogens; D009153:Mutagens; D012556:Schistosomicides