Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster.

Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction.

Delayed fertilization and chromosome anomalies in the hamster embryo.

Polyploidy and aneuploidy in hamster embryos are produced as manifestations of pregnancy wastage in surviving young when the interval between the estimated time of ovulation and copulation and hence fertilization is progressively increased. Significant delays resulted in triploidy in runted embryos, and the sporadic occurrence of mosaic aneuploidies.

Chromosome mutations and pH disturbances.

Chromosomal anomalies, namely hypodiploidies, hyperdiploidies, and endoreduplications, developed in nearly 25% of metaphase plates of replicating human lymphocytes exposed in vitro to either acid (6.5 to 6.9) or alkaline (8.4 to 8.8) pH equilibriums. The G group was most susceptible to aneuploid formation. Mammalian mutations may develop as the result of a pH disturbance during cleavage of the fertilized zygote.

Sodium pentobarbital-induced mutations in the hamster.

When virgin Syrian hamsters aged 6 to 8 wk were mated during estrus and anesthetized with sodium pentobarbital (Nembutal) 4 to 5 hr before estimated ovulation, pregnancy wastage in the newly conceived litter was observed. This was manifested by polyspermy of moribund eggs and death of fertilized eggs, deficits of expected zygotes, and triploidy and tetraploidy in 3-day-old surviving embryos. Multiple factors determined the nature of this wastage, including dosage of Nembutal [sodium 5-ethyl-5-(1-methyl butal) barbiturate], route of its administration, degree of resulting respiratory depression, and ultimately a pH imbalance (below 7) in the mother. Polyspermy appeared to result from the penetration of degenerating ova by 10-20 sperm, triploidy to polar body retention, and tetraploidy to endoreduplication of chromosomes before cell cleavage; identification of 2N/4N mosaics supports this inference.

A mortality study of carbon black workers in the United States from 1935 to 1974.

In a retrospective cohort study, the observed mortality of employees of four United States carbon black producters was compared with that expected on the basis of population death rates of the states in which the plants were located. Of 190 deaths among carbon black workers, 29 were due to malignant neoplasms and 89 were due to heart disease. Observed deaths of workers did not exceed expectation in any of the diagnostic categories examined. The results of this study suggest that exposure to carbon black does not increase workers' risk of mortality from malignant neoplasms of heart disease above those of the populations from which they are drawn.

Trisomies and triploidies in hamster embryos: induction by low-pressure hypoxia and pH imbalances.

The authors produced trisomic and triploid embryos by mating hamster females approximately 1 hr before estimated ovulation and subsequently submitting them to low-pressure atmospheres equivalent to those found at mountain altitudes for 6 hr. During hypoxic exposures in the low-pressure chamber, the continuous monitoring of pH levels--both subcutaneously and intramuscularly--registered pH decreases from inital values as high as 7.6 to below 6.9. These findings indicate that trisomies in some embryos and triploidies in others have their origin in different, but related mechanisms involving maternal pH imbalances between ovulation and fertilization.

Hypoxia and induced mutations in Syrian (golden) hamsters. The origin and perpetuation of a species.

We were able to identify anomalous chromosome patterns-monosomy, trisomy, and polyploidy-in metaphase plates prepared from embryos of Syrian hamsters (Mesocricetus auratus) whose mothers had been exposed to low-pressure hypoxia during the hours after copulation. These females were exposed in a low-pressure chamber for 4 hours at pressures equivalent to 30,000 feet of altitude before (estimated) ovulation to create acid shifts of pH equilibrium in the milieu of newly released eggs during passage of sperm upward, during fertilization itself, and during early cleavage stages. The D group chromosomes were most frequently involved in both monosomy and hyperdiploidy. The easily identifiable X chromosome also appeared to be susceptible to aneuploid formation. Chromosomally abnormal patterns most frequently among sibling embryos conceived by aging mothers exposed to low-pressure hypoxia. The significance of induced mutations is discussed.