Hemopoietic stem cells in murine embryonic yolk sac and peripheral blood.

Disaggregated embryonic yolk sac cells and circulating peripheral blood cells were obtained from normal murine day 9 embryos, prior to the formation of the fetal liver. These cells were microinjected transplacentally into days 11-15 W mutant anemic fetuses, when the fetal liver was the major hemopoietic organ. In a small proportion of the recipient animals examined after birth, long-term repopulation by the embryonic donor hemopoietic cells was observed. The donor hemopoietic stem cells proliferated and differentiated in the hosts as evidenced by the presence of donor hemoglobins in the growing recipient host animals. Some mothers of the pups were also repopulated by the donor stem cells. These results provide direct evidence that, during early murine embryogenesis, there are functional hemopoietic stem cells which are capable of colonizing the adult hemopoietic organs and probably the fetal liver and spleen to initiate hemopoiesis in these tissues.

Genotype- and age-associated in vivo cytogenetic alterations following mutagenic exposures in mice.

We studied mice from eight genetic strains at two ages (young, 10 weeks; and old, more than 80 weeks) for cytogenetic alterations (sister chromatid exchange (SCE), micronuclei, and metaphase indices) following challenges by two known mutagens: N-nitrosoethyl urea (ENU, 17 mg/kg) and cyclophosphamide (CP, 4.5 mg/kg) on bone marrow cells in vivo. The data were used to evaluate the effect of age, genotype, and differential aging patterns of genotypes in relative susceptibility to chromosomal breakage and instability in otherwise normal individuals. The older animals had a higher frequency of micronuclei, reduced metaphase indices, and lower SCE/cell as compared with their younger counterparts. Treatment with both mutagens significantly increased micronuclei and SCEs/cell in almost all strains at both ages but had little effect on the frequency of cells in metaphase. Among individual differences for SCEs/cell at most treatment combinations were not significant. In general, the induced SCEs (treatment-control) are significantly higher in older animals, variable among strains, and relatively higher as a result of CP than the ENU treatment. When the age effect was evaluated as the difference of SCE/cell in old and SCE/cell in young animals of each genotype-treatment combination, an age-dependent pattern was evident. In the presence of a mutagen the pattern in aging response was highly variable and strain (genotype) dependent. This variability may be viewed as subtle inherent genetic predisposition of sensitivity to mutagens that could be evaluated only using sensitive measures (e.g., SCE and not micronuclei) following more than one mutagenic challenges. These subtle differences could become pronounced when these parameters are evaluated at different ages on the same genotype.(ABSTRACT TRUNCATED AT 250 WORDS)