Increased incidence of developmental anomalies among descendants of carriers of methylenebisacrylamide-induced balanced reciprocal translocations.
N,N'-Methylenebisacrylamide (MBA), a dimer of the monomeric acrylamide, was studied for induction of clastogenic effects in germ cells of male mice. It was found to be effective in inducing dominant-lethal mutations and heritable translocations in maturing sperm. The semisterile translocation carriers and their normal counterparts were used to determine the health impact of transmitted chromosomal rearrangements through anatomical analysis of their immediate descendants in utero. As expected, semisterility resulted primarily from embryonic death during the periimplantation stages presumably caused by sperm segregants with unbalanced chromosome complement fertilizing some of the eggs. Among conceptuses that survived to mid- and late-gestation stages, there was an increased incidence of developmental anomalies including fetal death and phenotypic defects. These anomalies are assumed to be caused by certain types of unbalanced segregants that are compatible with survival beyond the periimplantation period. This class of unbalanced segregants represent in humans a major health problem to the mother and her conceptus.
Rutledge
J C
JC
Department of Laboratories, Children's Hospital and Medical Center, University of Washington School of Medicine, Seattle 98105.
Cain
K T
KT
Kyle
J
J
Cornett
C V
CV
Cacheiro
N L
NL
Witt
K
K
Shelby
M D
MD
Generoso
W M
WM
D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D005260:Female; D015321:Gene Rearrangement; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation; D013094:Spermatozoa / Q000187:drug effects*; D014178:Translocation, Genetic
D000178:Acrylamides; C021221:N,N'-methylenebisacrylamide