The latent period in carcinogenesis by plastics in rats and its relation to the presarcomatous stage

Early development of injection-site sarcomas in rats: a study of tumours induced by a rubber additive.

“…In the 1930's, foci of " abnormal fibroblasts ", " atypical spindle cells ' or " abnormal granulation tissue" were recorded in rats and mice bearing subcutaneous implants of 3,4-benzopyrene, 3-methyleholanthrene or 7,12-dimethylbenz(a)anthracene (Rondoni, 1937;Orr, 1939;Stewart, 1939), and this earlier work was later confirmed and extended by Vasilief and his colleagues (Vasilief, 1959;Vasilief et al, 1962). More recently, similar changes have been observed in association with iron-dextran (Baker et al, 1961;Roe and Carter, 1967;, and with various implanted plastics (Oppenheimer et al, 1958(Oppenheimer et al, , 1964 Roe, Dukes and Mitchley, 1967).…”

“…Although there is convincing evidence that some of these nodules later invade the surrounding tissues, it is not established (a) whether the formation of early sarcomatous nodules is an essential intermediate stage before invasive lesions develop, or (b) how many of these early nodules become invasive. It is almost certain that not all foci of (presumptive) neoplastic cells develop into overt sarcomata, a view which is supported by the transplantation experiments of Stewart (1939) and by more recent observations by Oppenheimer et al (1964). These workers showed that cellophane implanted into rats induced abnormal fibroblastic proliferation much earlier than implants of other plastics (4-5 weeks instead of 5-6 months); despite this premature activity, overt sarcomata induced by cellophane films did not appear significantly earlier and the eventual yield of macroscopic tumours was no greater.…”

Prevalence of heteroploidy in plastic film-induced primary sarcomas.

“…In addition, an altered oxygen supply itself has been reported to cause a derangement of the mitotic mechanism and this may lead to various chromosomal changes in the daughter cells (Gavaudan, 1956). Since the sarcomas apparently arise in an area of hyalinized avascular fibrous tissue (Oppenheimer et al, 1958), the wide variety of chromosomal rearrangements observed during this study may not be unexpected. Several processes that may lead to chromosomal aberrations are known, e.g., endomitosis, non-disjunction and chromatid breaks (Levan, 1956).…”

Induction of sarcomas in rats by solid and fragmented polyethylene: experimental observations and clinical implications.

“…It has been repeatedly shown that subcutaneous implants of solid plastics are soon enclosed in a pocket of fibrous tissue and that tumours eventually develop from elements in the walls of such pockets (Oppenheimer et al, 1952(Oppenheimer et al, , 1955(Oppenheimer et al, , 1959Oppenheimer, Oppenheimer, Stout, Willhite and Danishefsky, 1958). Powdered plastics are not encapsulated in this fashion (Oppenheimer et al, 1959(Oppenheimer et al, , 1961 and it is generally held that this is the main reason for their lack of carcinogenic activity.…”

“…One of the most compelling arguments in favour of the participation of physical factors in this context is that the carcinogenic activity of several plastics is either lost or greatly reduced if the same amount of material is implanted in the animal as a powder (Nothdurft, 1955;Oppenheimer et al, 1955;Oppenheimer, Oppenheimer, Stout, Danishefsky and Willhite, 1959;Oppenheimer, Willhite, Danishefsky and Stout, 1961).…”