1. Feeding 2-aminoanthraquinone (2-AAQ) in the diet to Fischer rats led to nephrotoxicity in females, caused by deposits of crystalline material in the kidney tubules. 2. This material consisted of 2-AAQ, N-acetyl-2-AAQ and N-formyl-2-AAQ. N-Formyl-2-AAQ was also identified in the ether extract of urine of rats fed 2-AAQ. 3. This represents the first case of identification of the N-formyl derivative of a primary aromatic amine as a metabolite in vivo.

A 20 d drug regimen of aminosidine (= paromomycin) at 12 mg/kg/d in combination with sodium stibogluconate at 20 mg/kg/d proved efficacious and well-tolerated in patients with visceral leishmaniasis in the State of Bihar, India. Eighteen of 22 evaluable patients achieved an ultimate cure. The remaining 4 patients, although not cleared of parasites, had their parasite grade reduced and also improved clinically. This confirms prior findings in Kenyan patients with kala-azar, and indicates that this regimen is a valid alternative to antimonial compounds alone in the State of Bihar, where cases of kala-azar not responding to antimonial drugs and intolerant of pentamidine are increasingly recorded.

Summary.-Male mice of inbred strains Swiss and C17 were fed daily 5 times a week by intragastric tube 0-1 ml of betel-nut aqueous extract, betel-leaf aqueous extract and the polyphenol fraction of betel nut. Male mice of corresponding strains fed 0.

Betel quid ingredients--betel nut, betel leaf, lime, catechu and tobacco--were tested separately and in various combinations for carcinogenicity, using hamster cheek pouch as the experimental site. The four modes of administration used were (1) tri-weekly painting of the cheek pouch with aqueous extracts of test materials, (2) deposition of replaceable wax pellets containing the test material, (3) gelatin capsules containing the powdered material and (4) insertion of natural material into the pouch for trauma and direct exposure. Untreated controls and standard carcinogen DMBA-treated controls were also maintained. A total of 317 young adult golden Syrian hamsters (Mesocricetus auratus) used for the experiments were killed in two age groups: 6-12 months and 13-24 months, only when signs of general debility were observed. In the untreated controls, animals were free of any malignancy. In the experimental series, various betel quid ingredient combinations under test induced both oral and gastric lesions ranging from massive atypia and precancerous lesions to frank carcinomas. Maximum lesions were observed in the groups receiving betel nut, lime and tobacco combinations and in the polyphenol fraction of betel nut containing major tannins. The mode of administration of test material resulted in distinct differences; tri-weekly paintings giving oral lesions in the range of 22-23% and gastric lesions 39-48%; the same material given either through the replaceable gelatin capsule or in natural form induced 69% oral lesions and 63 to 82% gastric lesions. Overall evaluation of the data of all the four series confirms the potent carcinogenicity of betel nut, particularly its tannin-containing polyphenolic fraction and its combination with lime and tobacco. Maximum oral lesions induced in the hamsters by continuous exposure to capsules and natural material, highlight the direct relationship of frequency of chewing in habitual chewers with oral carcinogenesis. The high incidence of gastric (forestomach) lesions invites special attention.

Sun-dried Mangalore betel nut extracts in water and in DMSO, and sun-cured Vadakkan tobacco extract in DMSO, were tested for their carcinogenic potency. Inbred Swiss and C17 mice and golden hamsters were used for the experiments. Control animals treated with either DMSO or water did not show any changes at the sites of administration. On subcutaneous administration of betel nut extract, 60% of Swiss mice developed transplantable fibrosarcomas at the site of injection. Skin application of DMSO extracts of tobacco and of betel nut separately did not result in skin lesions in C17 mice; but when a mixed DMSO extract of tobacco and betel nut was used, skin papilloma and epidermoid carcinoma developed in some animals. Similarly, hamster cheek pouches painted with a DMSO extract of tobacco alone did not develop malignant atypia whereas those painted with a DMSO extract of betel nut showed early malignant changes. DMSO extract of a mixture of tobacco and betel nut positively increased the incidence of early malignant changes in the hamster cheek pouch, indicating the enhancing effect of betel nut in carcinogenesis.