Premium
Comparative study of lung carcinogenesis, promoting action in leukaemogenesis and initiating action in skin tumorigenesis by urethane, hydrazine and related compounds
Author(s) -
Mirvish S. S.,
Chen Louise,
HaranGhera Nechama,
Berenblum I.
Publication year - 1969
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910040309
Subject(s) - carcinogen , carcinogenesis , methylhydrazine , chemistry , hydrazine (antidepressant) , lung , molar concentration , pharmacology , biochemistry , toxicology , medicine , biology , medicinal chemistry , organic chemistry , gene , phenylhydrazine
Urethane, N‐hydroxyurethane, hydrazine and some related compounds were tested in C57BL/6 and SWR 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 was 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 as 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 hydroxycarbamate showed a definite but short‐lived effect, and n ‐propyl carbamate was almost inactive. The results suggest that hydroxycarbamates exert a direct action on thymus weight, in addition to an action via conversion into the corresponding carbamates.