Comparative study of lung carcinogenesis, promoting action in leukaemogenesis and initiating action in skin tumorigenesis by urethane, hydrazine and related compounds
✍ Scribed by S. S. Mirvish; Louise Chen; Nechama Haran-Ghera; I. Berenblum
- Publisher
- John Wiley and Sons
- Year
- 1969
- Tongue
- French
- Weight
- 658 KB
- Volume
- 4
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Urefhane, N-hydroxyurefhane, hydrazine and sume related compounds were tested in C57BL/6 and S W R mice for activity as lung carcinogens, promoters of X-ray leukaemogenesis, and skin tumour initiators. Equimolar doses were used where possible. N-hydroxyurethane (ethyl hydroxycarbamate) was as strongly coleukaemogenic as urethane, and equally or less active than urethane as a lung carcinogen. Methyl and n-propyl hydroxycarbamates were inactive in all three tests, which suggests that the chemical specificity of urethane is not due to an ethyl-specific N-hydroxylating system. Acetylurethane showed considerable lung-carcinogenic and coleukaemogenic activities, and N-methoxyurethane (ethyl methoxycarbamate) and n-propyl carbamate showed weak lung-carcinogenic activities. Earlier reports that hydroxyurea is not a lung carcinogen were confirmed, but a weak coleukaemogenic effect war apparent. Hydrazine sulphate showed a weak but definite activity as lung carcinogen despite the low dose used, and on a molar basis appeared to be almost as active a s urethane. Methylhydrazine sulphate was inactive.
The effects of single injections on the thymus weight of C57BL/6 mice were compared for four of the test compounds. N-hydroxyurethane produced an earlier and stronger depression of thymus weight than urethane, n-propyl hydroxycarhamate showed a definite but short-lived effect, and n-propyl carbamate was almost inactive. The results suggest that hydroxycarbainates exert a direct action on thymus weight, in addition to an action via conversion into the corresponding carbamates.