Radiation-induced translocations in spermatogonial stem cells of Macaca fascicularis and Macaca mulatta

3 adult monkeys, one Macaca fascicularis and two Macaca mulatta, were whole-body irradiated with 1 Gy gamma-rays (60 Co). Reciprocal translocations induced in spermatogonial stem cells were scored as translocation multivalents in primary spermatocytes from 7.5 to 27.5 months after exposure. The translocation yields ranged from 4.1% at the earliest to 1.8% at the latest sampling interval. No significant differences were observed in the responses of the individual animals. A decline in the translocation frequencies with time after treatment was found in all 3 animals. The present data are different from those reported for testicular X-irradiation of the rhesus monkey Macaca mulatta (van Buul, 1980; Lyon et al., 1976) in that the translocation yields are higher. They are consistent with the results reported for testicular gamma-irradiation of the crab-eating monkey Macaca fascicularis (Matsuda et al., 1984, 1985). In view of the present results it appears unlikely that a species difference exists within the genus Macaca in the sensitivity of spermatogonial stem cells to the induction of translocations by ionizing radiation.     

The induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.     

γ-Ray-induced reciprocal translocations in spermatogonia of the crab-eating monkey (Macaca fascicularis)

The yield of translocations induced by γ-rays in the crab-eating monkey (Macaca fascicularis) spermatogonia were studied by cytological analysis in spermatocytes derived from them. The frequencies of translocations were 0.09% at 0 Gy, 1.9% at 1 Gy, 2.5% at 2 Gy and 1.3% at 3 Gy, showing a humped dose-response curve with a peak yield around 2 Gy. No remarkable inter-seasonal or inter-animal variations in the induction of translocation were observed. The frequencies in the crab-eating monkey were significantly higher than those in the same Macaca genus, the rhesus monkey (Macaca mulatta) (van Buul, 1976, 1980). This inter-species difference in radiosensitivity might be affected by the condition of spermatogonial stem cells at the time of exposure to radiation, depending on the seasonal change in spermatogenetic activity.     

Dose-response relationship of gamma-ray-induced reciprocal translocations at low doses in spermatogonia of the crab-eating monkey (Macaca fascicularis)

The yield of translocations induced by acute gamma-irradiation at low doses (0.25 and 0.50 Gy) in the crab-eating monkey's (Macaca fascicularis) spermatogonia was examined. The frequencies of translocations per cell were 0.53% at 0.25 Gy and 1.07% at 0.50 Gy. Over the low dose range from 0 to 1 Gy, the dose-response relationship for translocation yield was a linear one with a regression coefficient of 1.79 X 10(-2). To estimate the sensitivity to the induction of translocations in the crab-eating monkey's spermatogonia, the slope of the regression line was compared with those in other mammalian species. Consequently, over the low dose range below 1 Gy, the sensitivity of the crab-eating monkey's spermatogonia to translocation induction was similar to several mammalian species, the mouse. Chinese hamster, and the rabbit, but significantly higher than that of the rhesus monkey and lower than that of the marmoset.     

Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation

Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy.     

A comparative study of the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of the rhesus monkey (Macaca mulatta)

Frequencies of radiation-induced chromosome aberrations in spermatogonia, peripheral blood lymphocytes and bone-marrow cells of the rhesus monkey (Macaca mulatta) and in human blood lymphocytes, were determined at different exposures of X-rays. The dose-response curve for the induction of reciprocal translocations in spermatogonia suggested a “hump” at about 200 rad. The absolute frequencies of chromosome aberrations in somatic and germ cells of the rhesus monkey were low in comparison with most other mammalian species and the ratio between aberrations in the two tissues was 25 to 1 at the 100 rad level. Although the numbers of “effective chromosome arms” in man and rhesus monkey are similar (81 vs. 83), the rhesus monkey showed a lower rate of induction of dicentrics in blood lymphocytes than man at all doses, reaching statistical significance at the 300 rad level.     

Evidence for a lentiviral etiology in an epizootic of immune deficiency and lymphoma in stump-tailed macaques (Macaca arctoides).

A retrospective study determined that an epizootic of immune suppression and lymphoma in stump-tailed macaques (Macaca arctoides) that began in 1976 was associated with a horizontally spread lentivirus infection. This conclusion was based on serology, epidemiology, pathology, and virus isolation. The lesions found in the stump-tailed macaques were more compatible with lesions seen in SIV-infected rhesus than those seen in rhesus macaques infected with type D retroviruses. A lentivirus, isolated from a rhesus inoculated with lymph node homogenate from a stump-tailed macaque, was designed SIVstm and was pathogenic for rhesus macaques. The isolate was antigenically related to other SIVs as well as to HIV-1 and HIV-2. Two surviving stump-tailed macaques sent to another colony carried SIVstm latently for at least 7 years and disseminated it throughout that colony.     

Amino acids in the plasma of fasting Japanese monkeys (Macaca fuscata fuscata andM. f. yakui)

The plasma levels of 26 amino acids and related compounds were determined in five male and five female adult members of each of the two subspecies of Japanese monkeys,Macaca fuscata fuscata andM. f. yakui. Activities of L-asparaginase and histaminase in plasma were also measured.Numerous differences in amino acid levels between the sexes in the subspeciesfuscata were noted, with the female consistently exhibiting lower values. Few differences were observed between the sexes of the subspeciesyakui or between the two subspecies of Japanese monkeys. These monkeys were similar to other previously studied nonhuman primates in exhibiting measurable levels of 3-methylhistidine in plasma. There were numerous quantitative differences among Japanese monkeys and stump-tailed macaques, rhesus monkeys, chimpanzees, and man, with the Japanese monkeys usually exhibiting higher plasma levels.L-asparaginase activity was not detectable in these Japanese monkeys. Histaminase activity was similar to that previously measured in pig-tailed macaques and chimpanzees, lower than that in rhesus monkeys and stump-tailed macaques, and higher than that in man.     

Melioidosis in imported non-human primates

In 1969, five cases of melioidosis in three separate outbreaks were diagnosed in nonhuman primates in the United States. In the first outbreak, two stump-tailed macaque monkeys (Macaca arctoides) developed signs of the disease approximately 6 months after purchase. A third animal, a chimpanzee (Pan troglodytes), probably acquired its infection from one of these monkeys. Two other unrelated cases involving a pig-tailed monkey (Macaca nemestrina) and a rhesus monkey (Macaca mulatta) were diagnosed. These monkeys had been imported 3 years and 6 months, respectively, prior to the recognized onset of their disease. These cases represent the first known occurrences of spontaneous melioidosis in nonhuman primates in the United States.     

Blood groups of crab-eating macaques (Macaca fascicularis) demonstrated by isoimmune rhesus monkey (Macaca mulatta) sera.

Twenty-one isoimmune sera produced in rhesus monkey (Macaca mulatta) containing type-specific antibodies for simian-type red cell antigens were tested for their cross-reactivity with red cells from crab-eating macaques (M. fascicularis). The majority of the antisera gave cross-reactions determining polymorphisms in the red cells of crab-eating macaques, homologous to those of rhesus monkeys. These results attest to the close taxonomic realationship between the two species of macaques, and have the practical implication that isoimmune sera produced for blood typing can also be used for typing red cells from related species, as has been also observed in studies on apes.     

Dose-effect relationship for X-ray-induced reciprocal translocations in mouse spermatogonia following pretreatment with 3-aminobenzamide

The influence of 3-aminobenzamide (3-AB) pretreatment on the dose-response relationship for radiation-induced reciprocal translocations in mouse spermatogonial stem cells was studied. The results show that at doses of 3-10 Gy of X-rays the frequencies of translocations were higher in 3-AB-pretreated animals as compared to animals that received X-rays only. The 3-AB pretreatment was not effective at dose levels of 1 and 2 Gy. The shape of the dose-effect curve was similar to that obtained without 3-AB pretreatment, i.e., a humped curve, but the initial slope was clearly steeper and the position of the peak was shifted from 7 to 9 Gy. The effects observed can be explained by a 3-AB-mediated sensitization of normally radioresistant stem cells that are at the stage of stimulation to enter the mitotic cycle, thus increasing the population of radiosensitive spermatogonial stem cells.     

三种笼养灵长类活动时间分配的比较研究

采用焦点动物法和连续记录法对3种笼养灵长类活动时间分配进行比较研究。结果表明,川金丝猴Rhi-nopithecus roxellanae和熊猴Macaca assamensis用于休息的时间多于猕猴Macaca mulatta,移动时间则相反;川金丝猴和猕猴用于理毛的时间多于熊猴。不同性别年龄组之间的活动时间分配有差异,主要表现在川金丝猴母亲用于理毛的时间明显多于成年儿子,用于玩耍的时间则相反;猕猴成年雄性的移动时间和理毛时间多于成年雌性,玩耍时间则少于成年雌性;熊猴成年雌性的移动时间多于成年雄性,与成年个体相比,幼体花更多的时间用于玩耍,而相应的减少了其休息时间。     

Long-term effects of irradiation before adulthood on reproductive function in the male rhesus monkey.

Today, many patients, who are often young, undergo total body irradiation (TBI) followed by bone marrow transplantation. This procedure can have serious consequences for fertility, but the long-term intratesticular effects of this treatment in primates have not yet been studied. Testes and epididymides of rhesus monkeys that received doses of 4-8.5 Gy of TBI at 2-4 yr of age were studied 3-8 yr after irradiation. In all irradiated monkeys, at least some seminiferous tubule cross-sections lacked germ cells, indicating extensive stem cell killing that was not completely repaired by enhanced stem cell renewal, even after many years. Testes totally devoid of germ cells were only found in monkeys receiving doses of 8 Gy or higher and in both monkeys that received two fractions of 6 Gy each. By correlating the percentage of repopulated tubules (repopulation index) with testicular weight, it could be deduced that considerable numbers of proliferating immature Sertoli cells were killed by the irradiation. Because of their finite period of proliferation, Sertoli cell numbers did not recover, and potential adult testis size decreased from approximately 23 to 13 g. Most testes showed some dilated seminiferous tubules, indicating obstructed flow of the tubular fluid at some time after irradiation. Also, in 8 of the 29 irradiated monkeys, aberrant, densely packed Sertoli cells were found. The irradiation did not induce stable chromosomal translocations in spermatogonial stem cells. No apparent changes were seen in the epididymides of the irradiated monkeys, and the size of the epididymis adjusted itself to the size of the testis. In the irradiated monkeys, testosterone and estradiol levels were normal, whereas FSH levels were higher and inhibin levels lower when testicular weight and spermatogenic repopulation were low. It is concluded that irradiation before adulthood has considerable long-term effects on the testis. Potential testis size is reduced, repopulation of the seminiferous epithelium is generally not complete, and aberrant Sertoli cells and dilated tubules are formed. The latter two phenomena may have further consequences at still longer intervals after irradiation.     

Dose-response relationship for translocation induction in spermatogonia of the crab-eating monkey (Macaca fascicularis) by chronic gamma-ray-irradiation

The induction of reciprocal translocations in spermatogonia of the crab-eating monkey (Macaca fascicularis) by chronic gamma-irradiation (1.8 x 10(-5) Gy/min, about 0.024 Gy/22 h/day) was examined. The frequencies of translocation per cell were 0.15% at 0.3 Gy, 0.27% at 1.0 Gy and 0.33% at 1.5 Gy. The dose-response relationship for translocation yield was a linear one with a regression coefficient (b) of 0.16 x 10(-2). When the slope (b) of the regression line was compared with that at a high dose rate (0.25 Gy/min, b = 1.79 x 10(-2), it was clear that the induction rate of translocations after chronic gamma-irradiation was only about one-tenth of that after high-dose-rate irradiation. Thus, there was evidence for a pronounced dose-rate effect in the crab-eating monkey.     

Copulatory behavior in relation to anatomical characteristics of three macaques

Anatomy of copulatory organs and patterns of copulatory behavior were studied in three species of Macaca. The copulatory behavior of the rhesus monkey (M. mulatta) and crab-eating macaque (M. fascicularis) were similar. Mounting time was longer in stump-tailed macaque (M. arctoides) (48 seconds) than in the rhesus monkey or crab-eating macaque (8.5 seconds). Species differences were correlated with anatomical differences in the female and male reproductive organs. In the stump-tailed macaque the male has a relatively long penis, and the female has an elaborate vestibular colliculus in the vestibule. Both rhesus and crab-eating macaques have a short penis, and the female has no vestibular colliculus. Under scanning electron microscope, cone-like projections (3–4 mm) were observed on the surface of the glans and corpus penis of M. arctoides. In M. fascicularis shorter projections (0.05–0.1 mm) were observed on the glans penis but not the corpus penis.     

Weights and heights of stump-tailed macaques (Macaca arctoides) living in colony groups.

Weights and heights of adults, week-old infants, and animals of intermediate ages were obtained from colony groups of stump-tailed macaques and are compared with similar measurements of rhesus, Japanese macaques, and other stump-tailed monkeys.     

Phylogenetic relationships among Japanese, rhesus, Formosan, and crab- eating monkeys, inferred from restriction-enzyme analysis of mitochondrial DNAs [published erratum appears in Mol Biol Evol 1988 Sep;5(5):601]

Mitochondrial DNA (mtDNA) polymorphisms in four species of macaques, i.e., Japanese monkey (Macaca fuscata), rhesus monkey (M. mulatta), Formosan monkey (M. cyclopis), and crab-eating monkey (M. fascicularis), were analyzed to study phylogenetic relationships. When 17 restriction enzymes of 6-bp recognition were used, 42-49 sites were observed in the samples. The estimated number of nucleotide substitutions per site among Japanese, rhesus, and Formosan monkeys ranges from 0.0318 to 0.0396, and that between the crab-eating monkey and the other monkeys from 0.0577 to 0.0653. These findings suggest that the crab-eating monkey diverged from the other three approximately 1.5-3.0 Myr before the present (Mybp) and that the Japanese, rhesus, and Formosan monkeys diverged approximately 0.9-1.8 Mybp, although the branching order cannot be determined conclusively.      

Comparative anatomy and histology of the cervix uteri in non-human primates

The uterine cervix of rhesus macaque, crab-eating macaque, stump-tailed macaque, pig-tailed macaque, marmoset, baboon, patas, and squirrel monkeys was studied macroscopically and microscopically. Distribution of spermatozoa and leukocytes in the lumen and within the crypts and clefts was studied in rhesus and marmoset uterine cervix. The cervical canal of baboon, patas, marmoset, and stump-tailed monkeys is straight or slightly bent. The presence of variably developed ventral and dorsal colliculi in rhesus, crab-eating, and pig-tailed macaques causes the dorsoventral sinuosity of the cervical canal. The cervix of all investigated specimens is fundamentally fibrous tissue and the amount of muscle fibers increases toward the uterine corpus. The cervical mucosa of baboon, marmoset, and patas monkeys contains a large amount of clefts and tubular tunnels of variable structure, length, width, direction, and degree of branching. The cervical mucosa of macaques contains a large number of crypts of complex structure, length, width and degree of branching. The cervical crypts in macaques are usually longer in the ectocervix; whereas, in the midcervix, mucosa contains small crypts, clefts and long tunnels. Squamo-columnar junction is located near the external os in baboon, patas, marmoset, rhesus, crab-eating, and pig-tailed monkeys. In squirrel monkey, squamous epithelium is continuous through the external os, covers the vestibule and external surface of the cervical colliculi. In stump-tailed macaque, squamo columnar junction is located in the vagina, 1–3 cm from the external os of the cervix. The vaginal wall between the squamo-columnar junction and the external os of the cervix is covered with heavily branched mucosa lined with columnar epithelium. Ciliated cells of cervical epithelium occur in 9 to 19%. A large number of spermatozoa and a relatively low number of leucocytes have been found within crypts and clefts of cervical mucosa. The results are discussed in relation to the function of the cervix in different stages of the cycle, during pregnancy and parturition.This investigation was supported in part by Ford Foundation Grant No. 710-0287.     

Blood groups of pig-tailed macaques (Macaca nemestrina).

The human-type A-B-O blood groups of 57 pig-tailed macaques (Macaca nemestrina) were determined and the calculated gene frequencies, O = 0.8908, A = 0.0825 and B = 0.0267, gave excellent fit with the hypothesis of inheritance by triple allelic genes. In tests for simian-type blood groups with rhesus, baboon and crab-eating macaque immune antisera, it was shown that the red cells of pig-tailed macaques are polymorphic for several simian-type specificities defined by those cross-reacting sera. Pig-tailed macaques share with other macaque species the complex Drh-graded blood group system, which seems to occupy a special role among red cell antigens of macaques. Normal sera of three female macaques contained spontaneous isoagglutinins which selectively agglutinated the red cells of some pig-tailed as well as stump-tailed macaques.