K. Sundaram

The effect of hycanthone and maleic hydrazide on the frequency of micronuclei in the bone-marrow erythrocytes of mice

Male Swiss mice were assigned to 6 groups of either 3 or 4 animals each. 3 groups were given hycanthone methanesulfonate intraperitoneally, at 40, 80 or 120 mg/kg, respectively; the dose was repeated after an interval of about 24 h. At the same time 2 groups received maleic hydrazide at 100 or 200 mg/kg, and the remaining group was given dimethyl sulfoxide which was used as a solvent for both drugs. 6 h after the second injection, the mice were killed and bonemarrow preparations were made. Hycanthone induced a significant increase in the frequency of micronuclei in the polychromatic erythrocytes and suppressed the P/N ratio significantly. However, there was no dose-response relationship. Maleic hydrazide, on the other hand, failed to influence the incidence of micronuclei or the ratio of poly- to normo-chromatic erythrocytes.

Dominant lethal mutations in male mice fed γ-irradiated diet

Three groups of Swiss male mice were fed a stock ration or an unirradiated or irradiated (2·5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of pre-implantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice.

Failure of ethanol to induce dominant lethal mutations in wistar male rats

2 groups of Wistar male rats (6-7 weeks old) were given ethanol, 15% in drinking water, for 5 days. The level of ethanol was gradually raised to 20 and 30% resp. Both groups received ethanol between 15 and 20% or 15 and 30% continuously during 35 days. Another group was given 30% ethanol for a period of 4 days before mating started. In addition to a control group, which received no treatment, a positive control group of rats exposed to 200 R X-rays, was used. After the treatments, individual males were paired with virgin Wistar females (10-12 weeks) at weekly intervals, and 8 sequential pairings were undertaken. Females were examined for uterine contents and corpora lutea, 10-11 days after their separation from the males. The females mated with irradiated males showed a high incidence of dead implantations and reduction of live implantations. No significant differences in the number of dead, live and total implantations at pre- and/or post-implantation levels were observed among the control and the ethanolic groups, showing that ethanol did not induce any dominant lethal mutations in these Wistar male rats. In the light of studies on alcoholics and other recent data, a need to investigate, independently, the potential mutagenic effects of ethanol and alcoholic beverages is discussed.

Frequency of polyploid cells in the bone marrow of rats fed irradiated wheat.

Diets containing different proportions of non-irradiated or irradiated wheat were fed to Wistar rats for 1 or 6 wk. Cytological analysis of the bone marrow showed no significant difference in the frequency of polyploid cells in the rats fed non-irradiated or irradiated wheat diets, even when the treated wheat was fed to the rats within 24 hr of irradiation.

Evaluation of freshly irradiated wheat for dominant lethal mutations in Wistar rats.

Three independent, serially performed experiments involving acute and chronic feeding of freshly irradiated wheat (75 krad, gamma-irradiation) were carried out in Wistar rats. In the first experiment groups of 10 males were given wheat for 1 week; irradiated wheat was consumed by the animals within 24 h or irradiation. In the other two experiments feeding of males was continued for 6 (10 males per group) and 12 (13 males per group) weeks, respectively, and the irradiated wheat was fed within 7 days of irradiation. At the end of each treatment period each male was paired with 3 females for 7 days and sequentially at weekly intervals for 5 or 8 weeks. Females were killed and examined for live and dead implantations and corpora lutea. There were no differences between groups with regard to fertility nor was there any inter-group differences as regards pre- and post-implantation losses whether the rats were fed irradiated or non-irradiated wheat. This suggested that even feeding of freshly irradiated wheat does not induce any dominant lethal mutations in rats.

Effect of thymic irradiation on the development of new-born mice

SummaryAn x-ray dose of 900 rads to new-born strain A mice with partial shielding of the inferior extremities, results in death from a fatal wasting disease before they are 6 weeks old. Shielding of the thymic area during irradiation prevents the development of the disease. In addition, the wasting disease can be prevented in a high percentage of animals by transplantation of fresh thymus from new-born animals within 48 hours after irradiation. Transplantation carried out 2 weeks after irradiation is ineffective. Animals 4 to 6 days old at the time of irradiation do not develop the wasting disease. On the basis of these findings, the role of the thymus in lymphopoiesis and immunological capacity is discussed.

Effects of Neonatal Thymic Exposure to High Doses of X-irradiation

The thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals.