Historical Perspective Benzo[apyrene the Classic Chemical Carcinogen

in the latter part of the nineteenth century, workers in the paraffin refining, shale oil, and coal tar industries had high incidences of skin cancer. A possible cause emerged during the period 1915-1918 when Japanese scientists discovered that painting the ears of rabbits and mice with coal tar extracts produced tumors, some of which were malignant (Yamagiwa and fchikawa, 1918).

The subsequent search for the "coal tar carcinogen" by chemists and medical researchers is classic (Phillips, 1983; Osborne and Crosby, 1987). Starting in 1922, research by a team of British chemists at the Institute of Cancer Research in London culminated in the synthesis in 1930 of the first pure chemical compounds to demonstrate carcinogenic activity, dibenz[a,/z]anthra-cene (DBA), XXV, and its 3-methyl derivative (Kenne-way, 1930; Kenneway, 1955, references therein). After distilling and fractionating two tons of pitch from a "Gas, Light, and Coke Company," they ultimately isolated several grams of two C20HI2 polycyclic aromatic hydrocarbons. Three years later, Cook and co-workers (1933) synthesized for the first time benzo[a]pyrene and benzo[e]pyrene and proved them identical to these two "coal tar PAHs." Ultimate confirmation of the carcinogenicity of BaP came when all five survivors of a group of ten mice whose backs had been painted with synthetic BaP developed tumors; BeP was not carcinogenic (Cook et al., 1933). Subsequently, BaP was identified in carcinogenic extracts of ambient air particles (Leiter et al., f942; Leiter and Shear, 1943; Waller, 1952; Kotin, f954) and in chimney soot (Goulden and Tipper, 1949).

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