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Biomedical subjects

J Saidi

Publications and source records attributed to J Saidi.

5 recordsLinked to original sources

Promoting effect of snuff in rats initiated by 4-nitroquinoline-N-oxide or 7,12-dimethylbenz(a)anthracene.

A canal was surgically created in the lower lip of male Sprague-Dawley rats and used as a reservoir for moist snuff. A total of 230 animals were randomized into six groups, five containing 40 rats and one containing 30 rats. After 2 wk of recuperation, the animals were treated as follows. Group I was initiated with 7,12-dimethylbenz(a)anthracene 3 times/wk for 4 wk followed by cotton pellet administration. Group II was initiated with 7,12-dimethylbenz(a)anthracene for 4 wk followed by snuff twice a day, 5 days/wk. Group III received snuff twice a day, 5 days/wk. Groups IV and V were initiated with 4-nitroquinoline N-oxide 3 days/wk for 4 wk. Thereafter Group IV received a cotton pellet, and Group V rats were treated with snuff twice a day, 5 days/wk. Group VI received a cotton pellet once a day, 5 days/wk. Treatment of all groups continued for a maximum of 104 wk. Group V rats had a significantly lower mean survival time than did the other groups because of the development of lip sarcomas in 66% of the rats as compared with 23% in Group II and 26% in Group III. One rat in each of Groups IV and VI developed lip sarcomas. The incidence of sarcomas in Group V as compared with the other groups is statistically significant (P less than 0.05 to 0.001). Spindle cell proliferation, a possible precursor lesion of lip sarcoma, was found in five rats of Group II, seven of Group III, and four of Group V. These results show that snuff has strong promoting capability with regard to the development of lip sarcomas after 4-nitroquinoline N-oxide initiation, but not after 7,12-dimethylbenz(a)anthracene initiation. Snuff by itself caused three squamous carcinomas of the palate, two squamous cell papillomas of the lip, and ten lip sarcomas (in 38 rats as compared with one lip sarcoma in 30 control rats), showing snuff to be carcinogenic for the lip and oral cavity.

4-Nitroquinoline-1-oxide

Lack of promoting ability of snuff in rats initiated with 4-nitroquinoline-N-oxide.

In an experiment to evaluate the carcinogenicity and promoting capacity of snuff, a reservoir was created in the lower lip of male Sprague-Dawley rats. Groups of 30 rats were treated with snuff only (twice a day on five days a week), propylene glycol (solvent) three times weekly for four weeks, painting of the hard palate with 4-nitroquinoline-N-oxide (4-NQO) three times weekly for four weeks followed by snuff, 4-NQO only for four weeks, or cotton pellets only (twice a day on five days a week). The experiment was continued up to 108 weeks. High levels of tobacco-specific nitrosamines were found in the snuff (a commercial US brand). Rats treated with snuff only, 4-NQO followed by snuff and 4-NQO only had a significantly higher number of squamous-cell tumours and hyperplastic squamous lesions of the lip, oral and nasal cavity and forestomach than solvent or untreated controls. The total number of neoplasms was significantly higher in rats treated with snuff only and with 4-NQO followed by snuff in comparison to the other groups. Thus, snuff and 4-NQO by themselves can induce benign and malignant tumours. Snuff appears to have a general tumorigenic effect but lacked promoting ability after initiation with 4-NQO.

4-Nitroquinoline-1-oxide

Snuff-induced carcinogenesis: effect of snuff in rats initiated with 4-nitroquinoline N-oxide.

A canal in the lower lip to function as a reservoir for snuff was surgically created in 150 male Sprague-Dawley rats. The animals were randomized into five groups of 30 each: Group I received snuff twice a day, 5 days a wk; Group II was painted with propylene glycol (solvent control) on the hard palate 3 times a wk during 4 wk; Group III underwent painting on the hard palate with 4-nitroquinoline N-oxide (4-NQO) dissolved in propylene glycol, 3 times a wk for 4 wk; Group IV received 4-NQO as in Group III followed by snuff application as in Group I; and Group V received a cotton pellet dipped in saline twice a day, 5 days a wk. Treatment continued for up to 108 wk. There was no significant difference in mean survival time between the groups. Squamous cell tumors of the lip, oral and nasal cavities, esophagus, and forestomach were seen only in Groups I, III, and IV. Nine tumors of these organs were found in Group I (six carcinomas and three papillomas), nine in Group III (seven carcinomas and two papillomas), and ten in Group IV (eight carcinomas and two papillomas). The difference between each of these groups and the control groups (II and V) with regard to tumor incidence is statistically significant (P less than 0.05). In Group I, four oral cavity or lip carcinomas were found in 29 rats, a significant difference in relation to control rats (P less than 0.05). In addition, hyperplastic lesions of the lip, palate, and forestomach were significantly more common in Groups I and IV compared with Groups II, III, and V. The study has shown that snuff and 4-NQO by themselves have the potential to induce malignant tumors. Initiation with 4-NQO followed by snuff did not significantly enhance tumor formation.

4-Nitroquinoline-1-oxide

The effects of acetaminophen, antipyrine and phenacetin on rat urothelial cell proliferation.

Abuse of combination analgesics containing phenacetin, antipyrine (phenazone) and caffeine have been associated with urinary tract tumors. Phenacetin and antipyrine have been shown to be promoters of urinary tract carcinogenesis and antipyrine is also a weak urinary tract carcinogen. Acetaminophen, the main metabolite of phenacetin, is one of the most commonly used analgesics in the USA. In the present study, the dose-related effect on the cell proliferation of the urothelium was evaluated in male Sprague-Dawley rats by autoradiography. Nine groups of twenty, 6-week old rats were treated with 0.5%, 1.0% or 1.5% of acetaminophen, antipyrine or phenacetin in the diet. A tenth group of rats received control diet without added chemicals. Ten rats from each group were killed after each of 6 and 12 weeks of feeding. There was a dose-related increase in the labeling index in the urothelium of the bladder and kidney, particularly after 6 weeks of drug administration. In particular, the 1.0% and 1.5% dose levels of antipyrine and phenacetin showed a marked proliferative effect on the urothelium. In the bladder after 6 weeks, the labeling indices were significantly increased. After 12 weeks, although numerically increased, the indices were not statistically significant. In the renal pelvic urothelium the labeling index was significantly increased in antipyrine and phenacetin treated rats at doses of 1.0% and 1.5%. After 12 weeks the majority of rats treated with 1.5% antipyrine and phenacetin had labeling indices greater than or equal to 2-fold than the control rats both in the kidney and bladder. The increased labeling indices were associated with urothelial hyperplasia, in particular after 6 weeks. In the rats treated with antipyrine there were significant degenerative changes in the urothelial cells expressed as marked vacuolization. The vacuolization is considered to be a toxic effect and the beginning of cell death. Thus cell death with regeneration may be responsible for the increased labeling index in the antipyrine groups. High doses of antipyrine were also associated with renal papillary necrosis in 50% of the rats.

Acetaminophen