RESUMO
An alkylating derivative of a hydrocarbon, 10-chloromethyl-9-chloroanthracene, gave rise to reduced numbers of chemically induced pulmonary adenomas in strain A mice enzootically infected with Sendai virus, while in the case of 7,12-dimethylbenz(a)anthracene, the opposite relationship was observed. Therefore, the presence or absence of viral infection was demonstrated to have a strong influence on carcinogenic susceptibility.
Assuntos
Neoplasias Experimentais/induzido quimicamente , Infecções por Paramyxoviridae/complicações , 9,10-Dimetil-1,2-benzantraceno , Animais , Feminino , Neoplasias Pulmonares/induzido quimicamente , Camundongos , Camundongos Endogâmicos , Vírus da Parainfluenza 1 Humana/patogenicidadeRESUMO
Carcinogenic bromomethyl- and chloromethylanthracenes and benz(a)anthracenes were found to react rapidly in vitro with DNA under physiological conditions and to varying degrees with nucleotides and nucleosides. The compounds were assayed for production of lung adenomas in strain A mice and relative carcinogenic potencies were compared with in vitro alkylation and with in vitro solvolysis rates. Success at quantitative correlation with carcinogenic potency was not obtained with either in vitro parameter. However, comparable noncarcinogenic compounds lacked their marked in vitro reactivity with DNA. Some potential polynuclear electrophiles, including chloromethyl derivatives of acridine and benz(c)acridine, a hydroxymethyl and an acetoxymethyl derivative of benz(a)anthracene, an acetoxymethylanthracene, and an acridinylglycine ester, were found not to be carcinogenic in the lung adenoma test.
Assuntos
Alquilantes , Carcinógenos , DNA , Adenoma/induzido quimicamente , Animais , Fenômenos Químicos , Química , Feminino , Neoplasias Pulmonares/induzido quimicamente , Camundongos , Relação Estrutura-AtividadeRESUMO
Simple alkylating derivatives of polycyclic aromatic hydrocarbons have been found to be much more carcinogenic in the Strain A mouse than are the parent hydrocarbons. It has also been shown that the carcinogenicity of these halomethyl hydrocarbons is not a function of the first-order solvolysis rate. The acridine antitumor agent and mutagen ICR 170, 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]acridine dihydrochloride, has been shown to be a potent carcinogen in the same system when administered i.v., superseding data in the literature indicating inactivity when the drug is administered i.p. Stimulation of the immune system has been shown to have a marked inhibitory effect on the carcinogenic activity of this compound.
