ABSTRACT A Chinese hamster with a single X chromosome was found in 23 off- spring from crosses between a male heterozygous for T(1;3)8Idr translocation and karyologically normal females. All karyotypes of cells from various tissues of this animal were 21,X. The animal had an external genitalia generally characteristic to the female but no typical proestrous and estrous figure was found in the vaginal smear, and the animal showed no indication of pregnancy by any crosses. On autopsy, two gonads were found. Microscopically, there were some large fluid-filIed cysts and many follicle-llke bodies in the cortex of both gonads, but no mature follicle containing an oocyte was observed. The XO conditions in the Chinese hamster are compared with those of other mammals.
ABSTRACT Mouse embryo limb bud (LB) and midbrain (MB) cells were prepared from day 10 mouse embryos and cultured as micromass cell islands for 5 days. Dif- ferentiation was determined by the number of stainable foci of differentiated cells, and the concentration at which each compound inhibited the formation of differ- entiated foci by 50 % of the control value (ICs0) was estimated according to the method by Flint and Orton (1984). The values of ICs0 of L-dopa, which is known as a teratogen, were 24 pg/ml in LB cultures and 12 pg/ml in MB cultures, respec- tively. Teratogenic hazards of three mycotoxins were compared in this system. Chaetochromin A and chaetochromiri D, which were new naphtho-y-pyrone dimers produced by Chaetomium sp., indicated strong inhibition (ICso 0.13-0.24 pg/ml) in LB and MB cell cultures, and ustilaginoidin A, which was a naphtho-y-pyrone dimer produced by Ustilaginoidea virens, inhibited at higher concentration than chaetochromins by several-folds in LB and MB cultures.
ABSTRACT When the fibroblast from a patient with Menkes kinky hair disease (MKHD) was cultured in a copper-enriched medium, the rounded, detached and floating cells increased in number. Cell proliferation was also inhibited consider- ably in the fibroblast from MKHD as compared to that from the normal con- trol. The fibroblast from hemizygote of the macular mouse showed a similar sensitivity for copper in culture medium. Copper content was significantly in- creased in the cultured fibroblasts from the patient with MKHD and the hemi- zygote of the macular mouse in a copper-enriched medium compared to that in the fibroblast from the respective control. These results were well identical to those in literatures concerning MKHD and indicate that the fibroblast from the hemizygote of the macular mouse biochemically show a close similarity to those from MKHD and that the macular mouse serves cellbiologically as a model of MKHD.
ABSTRACT The influence of endogenous or exogenous glutathione (GSH) on the teratogenicity of 5-fluorouracil (5-FU) was studied after a single intraperitoneal injection of 5-FU at a teratogenic dose (20 or 30 mg/kg) to ICR mice on day 11 of gestation. Pretreatment with intravenous GSH at 300 mg/kg, 5 minutes before 5-FU administration, decreased the incidence of oligodactyly induced with 5-FU and lowered the fetal mortality, but it did not prevent the decrease in body weight of fetuses. Pretreatment with intraperitoneal diethylmaleate, which decreases the level of endogenous GSH, at 350 mg/kg 6 hours before 5-FU administration in- creased the incidence of oligodactyly. Pretreatment orally with GSH at a dose of 300 mg/kg 30 minutes before intraperitoneal injection of 5-FU at 30 mg/kg to Wistar rats on day 13 of gestation decreased the frequency of limb malformations, but it did not prevent the decrease in body weight of fetuses.
ABSTRACT Congenital stapes footplate fixation is not so common in the clinical otology. The clinical features are the fixation of the stapedial footplate, and the consequent conductive hearing loss with flat curve at the level of 50 to 60 dB in air conduction since birth. Its familial occurrence have never been reported before. The authors found five these cases in one family. All five cases were females, two of whom were sisters and other three were cousins. Their mothers had not particular disturbances in the early stage of pregnancy. The sex-linked heredity was highly suspected in this familial occurrence. All the cases showed bilateral conductive hearing loss. Tympanotomies on all cases revealed no abnormality of the middle ear cavity, except that all the stapes were not mobile at the footplate in spite of the normal shape. Openings of a small fenestra onto the footplate were performed and teflon piston wire prostheses were used to reconstruct the new conducting route. The excellent improvement of postoperative hearing was gained in all the cases. Furthermore, out of family members another three cases with hearing loss were found. Pathogenesis was discussed in consideration of the developmental process of the stapes and histopathological findings in the previous reports.
ABSTRACT Data and considerations on the significance of establishing dose- response relationships in embryotoxicity (and especially teratogenicity) are presented here. The problems discussed include the following topics: - analysis and transformation of experimental data; - dose-response curves for various embryotoxic effects; - reproducibility of studies on prenatal toxicity; - prenatal versus maternal toxicity; - quantitative risk assessment; - “threshold” for teratogenic effects; - analyses of combinations of teratogens; - relationship between molecular events and chemical teratogenicity.