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1.
Cancer Res ; 41(12 Pt 1): 5027-32, 1981 Dec.
Article in English | MEDLINE | ID: mdl-7307005

ABSTRACT

A model system has been established for studying lung carcinogenesis using intratracheal instillation of 3-methylcholanthrene in C3H/AnfCum and C57BL/Cum X C3H/AnfCum F1 (hereafter called BC3F1/Cum) mice. The animals in these studies were screened for adventitious agents and were free throughout their lifetime of two important lung viruses, Sendai virus and pneumonia virus of mice. Under these conditions, the occurrence of spontaneous and chemically indiced lung cancers was determined over the lifetime of the animals. Data were analyzed by the actuarial method for lung tumor probability. Probability was found to be dose and time dependent. Over 95% of the 3-methylcholanthrene-treated BC3F1/Cum and over 88% of the C3H/AnfCum mice were found at death to have pulmonary carcinomas. Tumors observed in animals which died up to 40 weeks on test were almost always squamous cell carcinomas (approximately 85%), while tumors which were observed in animals which died after 50 weeks were mainly alveolar adenocarcinomas (approximately 80%). Both tumors types metastasized widely. Spontaneous lung cancers (only alveolar adenocarcinomas were observed) occurred in these two strains at low frequency and were expressed late in life. Thus, the system described affords a suitable model to study the induction, expression, and progression of lung tumors under conditions where a vast majority of animals develop neoplasia.


Subject(s)
Lung Neoplasms/chemically induced , Methylcholanthrene , Neoplasms, Experimental/chemically induced , Animals , Disease Models, Animal , Female , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Mice , Mice, Inbred Strains , Neoplasms, Experimental/epidemiology , Neoplasms, Experimental/pathology
3.
Cancer Lett ; 9(4): 277-84, 1980 Jun.
Article in English | MEDLINE | ID: mdl-7397681

ABSTRACT

C57BL/6Cum, DBA/2Cum, first filia (F1), and backcross progeny from these 2 parental strains of mice were evaluated for their susceptibility to 3-methylcholanthrene-induced lung cancers. In the crosses among these mice, aryl hydrocarbon hydroxylase (AHH) responsiveness segregated as a single autosomal dominant gene (the Ah locus). AHH responsive mice (Ahb allele) expressed 40-60 units AHH activity/g wet wt liver following intraperitoneal treatment with 3-methylcholanthrene (MCA) compared to AHH non-responsive mice (Ahd allele) which expressed 7-11 units AHH activity/g wet wt liver after MCA treatment. Intratracheal administration of 500 microgram MCA for a total of 4 times at weekly intervals yielded a variety of pulmonary cancers, including squamous cell carcinomas, alveolar adenocarcinomas, and adeno-squamous cell carcinomas among mice that survived 1 year after the carcinogen treatment. The AHH responsive C57BL/6Cum, F1, and C57BL/6Cum X F1 animals were much more susceptible to MCA-induced lung cancers than the AHH non-responsive DBA/2Cum mice. The lung cancers were also not randomly distributed in DBA/2Cum X F1 backcross progeny since significantly more lung cancers were found in AHH-responsive progeny than in AHH non-responsive mice. Data support genetic linkage between susceptibility to MCA-induced lung carcinomas and the Ahb allele.


Subject(s)
Aryl Hydrocarbon Hydroxylases/biosynthesis , Lung Neoplasms/chemically induced , Methylcholanthrene , Animals , Biotransformation , Enzyme Induction , Female , Liver/enzymology , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Methylcholanthrene/metabolism , Mice , Mice, Inbred Strains , Neoplasms, Experimental/chemically induced , Neoplasms, Experimental/genetics , Time Factors
4.
J Natl Cancer Inst ; 62(3): 561-4, 1979 Mar.
Article in English | MEDLINE | ID: mdl-105204

ABSTRACT

Inbred 4-week-old and 16-week-old SJL/J mice were treated sc with either 150 or 450 microgram 3-methylcholanthrene (MCA). No difference was noted in their subcutaneous tumor response related to age. Although the incidences of reticulum cell neoplasms (RCN's) were the same in the controls for the 2 age groups, more 16-week-old animals developed RCN's after carcinogen treatment than did 4-week-old SJL/J mice. More 16-week-old mice developed both subcutaneous tumors at the site of MCA injection and systemic RCN's than did mice treated at 4 weeks of age. This incidence was related to the coinciding of the chronologic age of the mice for RCN development with the latency for chemical carcinogen-induced subcutaneous tumor development. Mice treated with 7,12-dimethylbenz[a]anthracene at 16 weeks of age responded in the same way as did those treated with MCA.


Subject(s)
9,10-Dimethyl-1,2-benzanthracene/administration & dosage , Benz(a)Anthracenes/administration & dosage , Lymphoma, Large B-Cell, Diffuse/etiology , Methylcholanthrene/administration & dosage , Sarcoma, Experimental/etiology , Soft Tissue Neoplasms/etiology , Age Factors , Animals , Female , Injections, Subcutaneous , Mice , Mice, Inbred Strains
5.
J Natl Cancer Inst ; 62(3): 555-9, 1979 Mar.
Article in English | MEDLINE | ID: mdl-216841

ABSTRACT

The effects of sc administration of 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (BP) on spontaneous viral leukemia and subcutaneous sarcoma induction have been studied in weanling C58/J mice. MCA produced significantly more sarcomas at the inoculation site than did DMBA or BP; moreover, it interfered with leukemia development. DMBA produced fewer sarcomas, and the incidence of leukemia was comparable to that found in the controls. BP accelerated the incidence of leukemia, although no sarcomas were produced. When the effect of the age of the mice at the time of MCA treatment on the incidence of leukemia and sarcomas was studied, newborn and weanling mice were found to develop primarily sarcomas, whereas no sarcomas were produced in the 16-week-old mice, and 52-64% of the 16-week-old mice developed leukemia. The reason no sarcomas were found in the C58 mice was apparently different from the reason no sarcomas were found in AKR mice, inasmuch as the AKR mice did not live long enough for sarcomas to develop. Immunologic surveillance may have played a part in the sarcoma suppression in the C58 mouse.


Subject(s)
Carcinogens/administration & dosage , Leukemia, Experimental/etiology , 9,10-Dimethyl-1,2-benzanthracene/administration & dosage , Age Factors , Animals , Benzopyrenes/administration & dosage , Female , Injections, Subcutaneous , Leukemia Virus, Murine , Methylcholanthrene/administration & dosage , Mice , Mice, Inbred Strains , Sarcoma, Experimental/chemically induced , Soft Tissue Neoplasms/chemically induced , Tumor Virus Infections/etiology
6.
J Natl Cancer Inst ; 61(4): 1107-11, 1978 Oct.
Article in English | MEDLINE | ID: mdl-100603

ABSTRACT

Subcutaneous tumor induction with three dose levels of 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), and 7,12-dimethylbenz[a]anthracene (DMBA) in two vehicles was studied in C3H/Anf Cum, C57BL/6 Cum, DBA/2J, and (C57BLXC3H/Anf)F1 (BC3F1/Cum) mice. Median tumor dose levels were significantly lower when the three carcinogens were suspended in trioctanoin. When beeswax: trioctanoin (B:T) was used as a vehicle, the three carcinogens differed in their abilities to be absorbed or solubilized from the vehicle by the three strains of mice and the hybrid. In C3H/Anf mice, BP in B:T failed to produce tumors. In BC3F1 mice, no tumors were produced by MCA, BP, or DMBA in B:T. In C57BL/6 mice, no tumors were produced with DMBA or MCA in B:T. In DBA/2 mice, no tumors were produced by BP or MCA in B:T. These results indicated that the interpretation of tumor induction results obtained with B:T vehicle may be related to the conditions of bioassay rather than to the carcinogenic potential of a compound.


Subject(s)
9,10-Dimethyl-1,2-benzanthracene/administration & dosage , Bees , Benz(a)Anthracenes/administration & dosage , Benzopyrenes/administration & dosage , Caprylates/administration & dosage , Methylcholanthrene/administration & dosage , Soft Tissue Neoplasms/chemically induced , Triglycerides/administration & dosage , Waxes/administration & dosage , Animals , Female , Injections, Subcutaneous , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred DBA , Neoplasms, Experimental/chemically induced , Species Specificity
7.
Cancer Res ; 37(11): 3892-4, 1977 Nov.
Article in English | MEDLINE | ID: mdl-908029

ABSTRACT

The immunosuppressive effects of 3-methylcholanthrene (MCA) given intratracheally have been shown to correlate with susceptibility of some inbred strains of mice to MCA-induced carcinogenesis. In susceptible strains of mice, C3Hf and C57BL/6, intratracheal administration of MCA resulted in profound systemic immunodepression. This effect was not observed in resistant DBA/2 mice. This immunodepressive effect correlated with the inducibility of the aryl hydrocarbon hydroxylase enzyme complex and the inducibility of pulmonary tumors by MCA.


Subject(s)
Immunosuppressive Agents , Lung Neoplasms/chemically induced , Methylcholanthrene/pharmacology , Animals , Aryl Hydrocarbon Hydroxylases/metabolism , Female , Lung Neoplasms/enzymology , Lung Neoplasms/immunology , Male , Mice , Mice, Inbred Strains , Neoplasms, Experimental/chemically induced , Species Specificity
8.
Chem Biol Interact ; 13(3-4): 317-31, 1976 Jun.
Article in English | MEDLINE | ID: mdl-1269048

ABSTRACT

Pulmonary and hepatic levels of aryl hydrocarbon hydroxylase (AHH) were studied in inbred strains of mice following intratracheal (i.t.) instillation of 3-methylcholanthrene (MCA). I.t. instillation of 188 mug MCA in sterile 0.2% gelatin in saline resulted in preferential induction of pulmonary AHH. After treatment with this dose of MCA, the pulmonary AHH levels of strains C57BL/6Cum, C57BL/6J, BALB/cMai, C3H/fMai, and C57L/J were observed to be induced within 24 h after treatment. Strains DBA/2Cum, AKR/J, SJL/J, DBA/2J and RF/J expressed no such increase. At a dose of 500 mug MCA, the pulmonary tissue of DBA/2 mice did express a 4-fold increase. This increase in AHH was determined to be quite different from the increase observed in C57BL/6 mice by: (1) specific activity of the enzymes, (2) genetic regulation, (3) susceptibility to inhibition by 7,8-benzoflavone, and (4) spectral properties of the associated cytochromes. It was of major importance that induction of pulmonary AHH was observed to be regulated by a single dominant gene in crosses involving the C57BL/6Cum and DBA/2Cum strains of mice. Results were discussed with the view in mind that these genetically regulated levels of AHH may play a role in susceptibility to cancers induced by polycyclic aromatic hydrocarbon carcinogens.


Subject(s)
Aryl Hydrocarbon Hydroxylases/metabolism , Lung/enzymology , Microsomes, Liver/enzymology , Microsomes/enzymology , Animals , Flavonoids/pharmacology , Kinetics , Lung/drug effects , Methylcholanthrene/pharmacology , Mice , Mice, Inbred Strains , Microsomes/drug effects , Microsomes, Liver/drug effects , Species Specificity
20.
Science ; 177(4043): 60-1, 1972 Jul 07.
Article in English | MEDLINE | ID: mdl-4339425

ABSTRACT

The incidence of 3-methylcholanthrene-induced subcutaneous tumors was significantly reduced by a single injection of inactivated type C RNA viral vaccine. Rauscher leukemia virus vaccine reduced the incidence of sarcomas from 78 to 50 percent in the BALB/cCr mouse. Radiation leukemia virus vaccine and a vaccine from a wild murine leukemia virus derived from a 3-methylcholanthrene tumor reduced the incidence of sarcoma from 86 percent to 33 and 37 percents, respectively, in the C57BL/6 mouse. These reductions in tumor incidence by virus vaccines help support the concept that type C RNA viruses serve as determinants of chemically induced cancer; additional studies of vaccines made with more purified virus preparations are necessary.


Subject(s)
Carcinogens , Neoplasms, Experimental/prevention & control , Viral Vaccines/therapeutic use , Animals , Animals, Newborn , Antigens, Viral , Complement Fixation Tests , Female , Immunization , Leukemia Virus, Murine , Methylcholanthrene , Mice , Mice, Inbred Strains , Neoplasm Transplantation , Neoplasms, Experimental/chemically induced , Rauscher Virus , Retroviridae , Sarcoma/prevention & control , Spleen/immunology
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