Tests for chemical carcinogens: Report on the activity of derivatives of aromatic amines, nitrosamines, quinolines, nitroalkanes, amides, epoxides, aziridines, and purine antimetabolites

Tests for chemical carcinogens: Report on the activity of derivatives of aromatic amines, nitrosamines, quinolines, nitroalkanes, amides, epoxides, aziridines, and purine antimetabolites

Hadidian, Z; Fredrickson, TN; Weisburger, EK; Weisburger, JH; Glass, RM; Mantel, N

HERO ID

62691

Reference Type

Journal Article

Year

1968

Language

English

PMID

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HERO ID	62691
In Press	No
Year	1968
Title	Tests for chemical carcinogens: Report on the activity of derivatives of aromatic amines, nitrosamines, quinolines, nitroalkanes, amides, epoxides, aziridines, and purine antimetabolites
Authors	Hadidian, Z; Fredrickson, TN; Weisburger, EK; Weisburger, JH; Glass, RM; Mantel, N
Journal	Journal of the National Cancer Institute
Volume	41
Issue	4
Page Numbers	985-1036
Abstract	A technique suitable for mass screening of carcinogenic chemicals was developed. Male Charles-River-rats received doses of 38 carcinogens in log 10 increments for 8 weeks to determine lethal dose. The maximal tolerated dose (MTD) was determined by administration of 0.5 log intervals of the compounds by gavage 5 days per week. Male and female rats received the MTD and 5 doses at decreased intervals of 0.5 log and were treated 5 days per week for 52 weeks. Animals were observed for 6 additional months and autopsied, or autopsied at natural death prior to 6 months. Females receiving 30 milligrams of 2-naphthylamine (91598) died within 2 to 6 days, whereas males were not affected. Of the compounds tested, 10 were definitely carcinogenic causing ear duct tumors, skin papillomas, adenomas, polyps, intestinal adenocarcinomas, mammary adenocarcinomas in females, bladder tumors, tumors of the forestomach, and testicular tumors. These carcinogens included: N,N'-dinitroso-N,N'-diethylethylenediamine (7346147), 1,4-dinitrosopiperazine (140794), N,N'-dinitroso-N,N'-dimethyl-1,3-propanediamine (6972765) aphoxide (545551), 3-methyl-2-naphthylamine (10546244), 3-nitro-2-naphthylamine (13115281), 4-(p-dimethylaminostyryl)quinolone (897552), and 3,3'-dimethoxybenzidine (119904), N,4-dinitroso-N-methylaniline (99809), and 2-(4-dimethylaminostyryl)benzothiozale (1628586). Neoplasms occurred in rats treated with 2-naphthylamine, 3-methyl-2-naphthylamine, dichloronitronaphthalene (52270663), 2-nitroso-1-naphthol (132536), dimethyl-p-dimethylaminostyrylquinolone (19716213), 8-quinolinol (148243), and azauracil (461892), but there was no certainty that they were induced by treatment. Some tumors of the lip, tongue, or esophagus were seen in animals receiving nitropropane (79469), aphoxide, nitrilotrispropronamide (2664611), dinitrosopentamethylenetetramine (101257), apholate (52460), azoxanthine (1468264), azathymine (932536), azaquanine (134587), and N-2-fluorenylacetamide (53963), but the significance could not be determined. The remainder of the compounds were negative for carcinogenicity. The authors conclude that a multidose study is useful.
Doi	10.1093/jnci/41.4.985
Pmid	5686039
Url	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0014348266&doi=10.1093%2fjnci%2f41.4.985&partnerID=40&md5=b6f6c452ec66427512d9d5963af41bf6
Is Certified Translation	No
Dupe Override	No
Comments	J. Natl. Cancer Inst. 41: 985-1036.
Is Public	Yes
Language Text	English
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