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D Coombs

Publications and source records attributed to D Coombs.

7 recordsLinked to original sources

Inhalation teratology and two-generation reproduction studies with 1,1-dichloro-1-fluoroethane (HCFC-141b).

HCFC-141b is one of the chemicals being considered as a replacement for CFC 11 in solvent and foam-blowing applications. Teratology studies were conducted in both rats and rabbits and a two-generation reproduction inhalation toxicity study was conducted in rats. The pregnant rabbits were exposed to levels of 0 (control), 1400, 4200 and 12,600 ppm HCFC-141b from day 7 to day 19 of gestation (6 hr/day). There was no evidence of developmental or teratogenic effects on the foetuses. The pregnant rats in the teratology study were exposed to levels of 0 (control), 3200, 8000 and 20,000 ppm from days 6 to 15 of gestation (6 hr/day). In the 20,000 ppm exposure group, there was an increase in implantation losses; furthermore, in this group, foetal weights tended to be lower than controls. As with the rabbits, there was no evidence of a teratogenic effect. The reproduction study was conducted at exposure levels of 0, 2000, 8000 and 20,000 ppm, 7 days/wk starting approximately 10 wk before the first pairing. Adult rats exposed at 20,000 ppm (and, to a lesser extent, those exposed to 8000 ppm) showed increases in water intake, slight increases in food consumption, and decreases in body weight. Following the mating of the F0 parents, there were fewer litters in the 20,000 ppm exposure level group than in controls. When these parents were then paired with different partners, again, the number of litters was lower in the 20,000 ppm group, although most of the animals that did not produce litters the first time mated successfully the second time. When the F1 animals were mated to produce the second generation, the number of litters was comparable for all groups. In the second F0 mating and the F1 mating, the number of pups per litter was lower at 20,000 ppm; although birth weights were comparable, body weight gain tended to be slower in the high-level exposure group. Survival was good in all groups. At 8000 ppm no significant effects were observed in the pups and only minimal signs in the adults. The 2000 ppm exposure level represented a clear no-observed-effect level for all indices.

Administration, Inhalation

7S-K nuclear RNA from simian virus 40-transformed cells has sequence homology to the viral early promoter.

Previous findings in our laboratory have identified a specific small nuclear RNA (7S-K) that promotes transcription initiation by RNA polymerase II in isolated mammalian nuclei. The present study was designed to investigate the homology between 7S-K RNAs and host and viral sequences in simian virus 40 (SV40)-transformed and in untransformed mouse 3T3 cells, with the object of testing the hypothesis that these RNAs take part in the transcription initiation complex by base pairing to promoter/enhancer regions of active genes. DNA . RNA hybridization experiments, using either Southern or RNA blotting techniques, indicated that both 7S-K and 7S-L RNAs hybridize to midrepetitive fractions of the mouse genome. However, only 7S-K RNA from transformed cells hybridized to SV40 DNA. Restriction mapping and nuclease S1 treatment of the hybridized region of SV40 yielded a 45-nucleotide-long hybrid duplex. Partial sequence analysis of the 5' end of the DNA in this duplex revealed sequence homology with the 21-base-pair repeat sequence, identified as the SV40 early promoter. Because the viral early gene is expressed in transformed cells, we conclude that 7S-K RNAs in these cells contain a species that has sequence homology to a promoter of an active gene. Taking these results together with previous ones, we postulate that the observed stimulatory activity of 7S-K RNA on transcription initiation is due to its recognition of promoter sequences, either to facilitate the formation or as part of the transcription initiation complex.

Animals