The use of a battery of strains of mice in a factorial design to study the induction of dominant lethal mutations.
The induction of dominant lethality following oral dosing of males with 200 mg/kg of cyclophosphamide was investigated using a factorial experimental design. Males from 3 genotypes, BALB/c, CBA/Ca and CBA/Ca X C57BL/6JF1 hybrid (CBB6F1) were mated to 6 females of the same genotype as the males over 3 weeks. Cyclophosphamide reduced the mating frequency of the BALB/c and CBA/Ca males. The total number of implants/female was reduced in all 3 genotypes with the greatest effect in the first 2 weeks after the males were treated. The proportion of early deaths/litter was significantly increased in CBA/Ca and CBB6F1 but the increase was smaller and non-significant with BALB/c. There was a high incidence (29.8%) of early deaths in the control BALB/c females. Statistical analysis of the ratio of early deaths to total implants in a litter using either the Freeman-Tukey binomial or the arc-sine transformation gave similar and satisfactory results. Analysis of early death data rather then the ratio of early deaths: total implants would have led to misleading conclusions. The implications of the use of a factorial design in dominant lethal assays for the detection of strain variation in mutagenic response without an increase in animal usage is discussed.
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects*; D005804:Genes, Lethal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL / Q000235:genetics; D008808:Mice, Inbred CBA / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics*; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D011897:Random Allocation
D009153:Mutagens; D003520:Cyclophosphamide