Search

In a controlled experiment groups of SPF Wistar rats were give 18 once-fortnightly doses of 0-5, 1-0 or 2-0 mg 3,4-benzpyrene (BP) suspended in infusine (I) or in carbon black (CB) + I by intratracheal instillation. Of rats examined post mortem, 1/16 given I+CB only, 0/16 given I only, 15/51 given BP in I+CB and 24/48 given BP in I developed squamous neoplasms of the lung. The incidence of tumours was significantly related to dose of BP. At the 1 or 2 mg dose levels BP in I only was more productive of tumours than BP in I+CB. Other changes encountered included squamous metaplasia of alveolar and bronchiolar epithelium (Sq.M), but not of bronchial epithelium, and cuboidal and columnar metaplasia of alveolar epithelium in the vicinity of terminal bronchioles (CCM). Sq.M was associated with exposure to BP or I+CB. CCM was strongly associated with exposure to I+CB but only weakly with exposure to BP.

SPF rats were exposed to the smoke from 10 cigarettes per week from the age of 10 weeks until they died. Survival, body weight, tumour incidence and histopathological appearances of the lungs were compared with those for untreated sham exposed rats. Two further groups were given a single dose of 3,4-benzyprene (BP) by intratracheal instillation. One of these was then exposed to the smoke of 10 cigarettes per week till death. Compared with untreated or sham exposed rats, exposure to smoke was associated with a significant reduction in incidence of mammary tumours. Exposure to smoke was associated with an increasing incidence of collections of macrophages laden with golden-brown pigment (GBM) and of areas of cuboidal or columnar metaplasia (CCM) or squamous metaplasia (Sq.M) of alveolar epithelium. In control rats there was virtually no GBM, a low incidence of CCM and Sq.M. Four out of 406 smoke exposed rats which came to post mortem had squamous neoplasms in the lungs, 3 having lesions of doubtful malignancy and one having a squamous carcinoma. In contrast, no squamous neoplasms were seen in 197 control rats. This difference was not statistically significant. The findings in rats given a single dose of BP were, in all the above respects, similar to those in untreated rats, except that one developed a squamous carcinoma of the lung. The effects of a single dose of BP followed by smoke exposure were in general similar to those of smoke exposure only. Three rats on this treatment regimen developed squamous cancers of the lung. None of the treatments increased the incidence of adenomata of the lungs. The results are discussed in relation to other studies of the effects of smoke exposure on rats and other species.

In a controlled experiment, 6 groups of SPF rats were given cigarette smoke condensate (SWS) in solid form without a vehicle once fortnightly by intratracheal instillation, at 3 dose levels with or without additional exposure to the vapour phase of smoke (VP) from 10 plain cigarettes each week. Treatment continued for life. Six other groups were similarly treated with one of 3 fractions of condensate with or without VP. Exposure to VP was associated with a significant reduction in body weight, but not signficantly with the incidence or severity of any observed pathological change in the lungs. A significant dose-related assoication was seen between SWS or its fractions and the incidence and degree of chronic respiratory disease (CRD), cuboidal or columnar metaplasia (CCM) and squamous metaplasia of alveolar epithelium (Sq.M) produced. No neoplasms, however, were elicited. A significant correlation was found between the degrees of CCM and of Sq.M produced in the 24 groups exposed to SWS or fractions. The results are discussed in the light of studies in which rats were exposed to tobacco smoke by inhalation and of studies in which the same condensate and fractions were applied to mouse skin.

The repeated intratracheal instillation of cigarette smoke condensate (SWS) in rats at close to maximum tolerated dose levels failed to induce squamous neoplasms in the lungs although such treatment was associated with an increased incidence of cuboidal/columnar metaplasia (CCM) and squamous metaplasia (Sq.M) of alveolar epithelium. With one exception, various fractions of SWS had no effect on lung tumour incidence though some were more effective than SWS in increasing the incidence of CCM and Sq.M. The exceptional fraction, Fraction P, which contains most of the polycyclic aromatic hydrocarbons of smoke and is the most effective of the fractions tested in producing tumours in mouse skin, gave rise to 4 squamous tumours of doubtful malignancy and one metastasizing squanmous carcinoma among 3 groups of 18 animals exposed at 3 different dose levels. The results are discussed in relation to the possible development of a method for comparing condensates for relative lung carcinogenicity.